DOI: 10.7554/elife.00780. Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA [Penn]

Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA

10.7554/elife.00780

Crossref journal-article

eLife Sciences Publications, Ltd

eLife (4374)

Abstract

Eukaryotes have two types of spliceosomes, comprised of either major (U1, U2, U4, U5, U6) or minor (U11, U12, U4atac, U6atac; <1%) snRNPs. The high conservation of minor introns, typically one amidst many major introns in several hundred genes, despite their poor splicing, has been a long-standing enigma. Here, we discovered that the low abundance minor spliceosome’s catalytic snRNP, U6atac, is strikingly unstable (t½<2 hr). We show that U6atac level depends on both RNA polymerases II and III and can be rapidly increased by cell stress-activated kinase p38MAPK, which stabilizes it, enhancing mRNA expression of hundreds of minor intron-containing genes that are otherwise suppressed by limiting U6atac. Furthermore, p38MAPK-dependent U6atac modulation can control minor intron-containing tumor suppressor PTEN expression and cytokine production. We propose that minor introns are embedded molecular switches regulated by U6atac abundance, providing a novel post-transcriptional gene expression mechanism and a rationale for the minor spliceosome’s evolutionary conservation.

Bibliography

Younis, I., Dittmar, K., Wang, W., Foley, S. W., Berg, M. G., Hu, K. Y., Wei, Z., Wan, L., & Dreyfuss, G. (2013). Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA. ELife, 2. CLOCKSS.

Authors 9

Ihab Younis (first)
Kimberly Dittmar (additional)
Wei Wang (additional)
Shawn W Foley (additional)
Michael G Berg (additional)
Karen Y Hu (additional)
Zhi Wei (additional)
Lili Wan (additional)
Gideon Dreyfuss (additional)

References 47 Referenced 79

10.1002/ajmg.a.34299 / Am J Med Genet A / A homozygous mutation in RNU4ATAC as a cause of microcephalic osteodysplastic primordial dwarfism type I (MOPD I) with associated pigmentary disorder by Abdel-Salam (2011)
10.1038/ng.556 / Nat Genet / Subtle variations in Pten dose determine cancer susceptibility by Alimonti (2010)
10.1093/nar/gkl796 / Nucleic Acids Res / U12DB: a database of orthologous U12-type spliceosomal introns by Alioto (2007)
10.1186/1471-2164-11-106 / BMC Genomics / U12 type introns were lost at multiple occasions during evolution by Bartschat (2010)
10.1186/1745-6150-3-19 / Biol Direct / U12 intron positions are more strongly conserved between animals and plants than U2 intron positions by Basu (2008)
10.1016/j.cell.2012.05.029 / Cell / U1 snRNP determines mRNA length and regulates isoform expression by Berg (2012)
10.1016/S0161-5890(02)00262-6 / Mol Immunol / Ribotoxic stress activates p38 and JNK kinases and modulates the antigen-presenting activity of dendritic cells by Bunyard (2003)
10.1016/S1097-2765(00)80292-0 / Mol Cell / Evolutionary fates and origins of U12-type introns by Burge (1998)
10.1111/j.1365-2567.2006.02347.x / Immunology / Dependence on p38 MAPK signalling in the up-regulation of TLR2, TLR4 and TLR9 gene expression in Trichomonas vaginalis-treated HeLa cells by Chang (2006)
10.1042/0264-6021:3510095 / Biochem J / Specificity and mechanism of action of some commonly used protein kinase inhibitors by Davies (2000)
10.1016/S0076-6879(06)11002-2 / Methods Enzymol / Analyzing micro-RNA expression using microarrays by Davison (2006)
10.1261/rna.1136108 / RNA / High-resolution gene expression profiling for simultaneous kinetic parameter analysis of RNA synthesis and decay by Dolken (2008)
10.1126/science.1202205 / Science / Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA by Edery (2011)
10.1093/cvr/cvp425 / Cardiovasc Res / Inactivation of the tumour suppressor, PTEN, in smooth muscle promotes a pro-inflammatory phenotype and enhances neointima formation by Furgeson (2010)
10.4049/jimmunol.176.9.5167 / J Immunol / Cutting Edge: Lentiviral short hairpin RNA silencing of PTEN in human mast cells reveals constitutive signals that promote cytokine secretion and cell survival by Furumoto (2006)
10.1006/excr.1996.0311 / Exp Cell Res / U6 snRNA maturation and stability by Fury (1996)
10.1126/science.271.5256.1716 / Science / Requirement of U12 snRNA for in vivo splicing of a minor class of eukaryotic nuclear pre-mRNA introns by Hall (1996)
10.1126/science.1200587 / Science / Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I by He (2011)
10.1038/sj.emboj.7600212 / EMBO J / Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125 by Heo (2004)
10.1093/nar/gni002 / Nucleic Acids Res / Detection and discovery of RNA modifications using microarrays by Hiley (2005)
10.1038/nature09479 / Nature / U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation by Kaida (2010)
10.1038/nmeth.1528 / Nat Methods / Analysis and design of RNA sequencing experiments for identifying isoform regulation by Katz (2010)
10.1083/jcb.152.1.157 / J Cell Biol / The Telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle by Kickhoefer (2001)
10.1016/j.cell.2007.09.043 / Cell / Splicing segregation: the minor spliceosome acts outside the nucleus and controls cell proliferation by Konig (2007)
10.1371/journal.pgen.0030212 / PLOS Genet / Extragenic accumulation of RNA polymerase II enhances transcription by RNA polymerase III by Listerman (2007)
10.1038/nmeth.1226 / Nat Methods / Mapping and quantifying mammalian transcriptomes by RNA-Seq by Mortazavi (2008)
10.1016/S1097-2765(02)00441-0 / Mol Cell / The divergent U12-type spliceosome is required for pre-mRNA splicing and is essential for development in Drosophila by Otake (2002)
10.1093/emboj/cdf297 / EMBO J / The splicing of U12-type introns can be a rate-limiting step in gene expression by Patel (2002)
10.1038/nrm1259 / Nat Rev Mol Cell Biol / Splicing double: insights from the second spliceosome by Patel (2003)
10.1152/ajpheart.00929.2011 / Am J Physiol Heart Circ Physiol / Regulation of phosphatase and tensin homolog on chromosome 10 in response to hypoxia by Qian (2012)
10.1093/bioinformatics/btq033 / Bioinformatics / BEDTools: a flexible suite of utilities for comparing genomic features by Quinlan (2010)
10.1038/nature05228 / Nature / An early evolutionary origin for the minor spliceosome by Russell (2006)
10.1128/MCB.24.5.1855-1869.2004 / Mol Cell Biol / An intronic enhancer regulates splicing of the twintron of Drosophila melanogaster prospero pre-mRNA by two different spliceosomes by Scamborova (2004)
10.1074/jbc.M511105200 / J Biol Chem / Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) mediates p38 MAPK stress signal-induced inhibition of insulin signaling. A cross-talk between stress signaling and insulin signaling in resistin-treated human endothelial cells by Shen (2006)
10.1093/nar/gkl556 / Nucleic Acids Res / Comprehensive splice-site analysis using comparative genomics by Sheth (2006)
10.1017/S1355838299982213 / RNA / Conservation of functional features of U6atac and U12 snRNAs between vertebrates and higher plants by Shukla (1999)
10.1038/nsmb.1666 / Nat Struct Mol Biol / Rates of in situ transcription and splicing in large human genes by Singh (2009)
10.1242/jcs.015230 / J Cell Sci / New insights into PTEN by Tamguney (2007)
10.1016/S0092-8674(00)81057-0 / Cell / A novel spliceosome containing U11, U12, and U5 snRNPs excises a minor class (AT-AC) intron in vitro by Tarn (1996)
10.1093/bioinformatics/btp120 / Bioinformatics / TopHat: discovering splice junctions with RNA-Seq by Trapnell (2009)
10.1038/nprot.2012.016 / Nat Protoc / Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks by Trapnell (2012)
10.1038/nbt.1621 / Nat Biotechnol / Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation by Trapnell (2010)
10.1002/wrna.1141 / Wiley Interdiscip Rev RNA / The significant other: splicing by the minor spliceosome by Turunen (2012)
10.1016/j.cell.2009.02.009 / Cell / The spliceosome: design principles of a dynamic RNP machine by Wahl (2009)
10.1016/j.molcel.2010.03.014 / Mol Cell / Gemin5 delivers snRNA precursors to the SMN complex for snRNP biogenesis by Yong (2010)
10.1128/MCB.01301-09 / Mol Cell Biol / Rapid-response splicing reporter screens identify differential regulators of constitutive and alternative splicing by Younis (2010)
10.1016/j.cell.2008.03.031 / Cell / SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing by Zhang (2008)

Dates

Type	When
Created	12 years ago (July 30, 2013, 2:12 p.m.)
Deposited	1 year, 10 months ago (Oct. 11, 2023, 8:40 p.m.)
Indexed	1 week, 2 days ago (Aug. 19, 2025, 6:04 a.m.)
Issued	12 years ago (July 30, 2013)
Published	12 years ago (July 30, 2013)
Published Online	12 years ago (July 30, 2013)

Funders 4

Howard Hughes Medical Institute 10.13039/100000011
Region: Americas
pri (Research institutes and centers)
Labels2
1. Howard Hughes Medical Institute Inc
2. HHMI
Association Française Contre les Myopathies
Howard Hughes Medical Institute 10.13039/100000011
Region: Americas
pri (Research institutes and centers)
Labels2
1. Howard Hughes Medical Institute Inc
2. HHMI
Association Française Contre les Myopathies

BibTeX

@article{Younis_2013, title={Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA}, volume={2}, ISSN={2050-084X}, url={http://dx.doi.org/10.7554/elife.00780}, DOI={10.7554/elife.00780}, journal={eLife}, publisher={eLife Sciences Publications, Ltd}, author={Younis, Ihab and Dittmar, Kimberly and Wang, Wei and Foley, Shawn W and Berg, Michael G and Hu, Karen Y and Wei, Zhi and Wan, Lili and Dreyfuss, Gideon}, year={2013}, month=jul }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        19
      ]
    ],
    "date-time": "2025-08-19T10:04:15Z",
    "timestamp": 1755597855905,
    "version": "3.41.2"
  },
  "reference-count": 47,
  "publisher": "eLife Sciences Publications, Ltd",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2013,
            7,
            30
          ]
        ],
        "date-time": "2013-07-30T00:00:00Z",
        "timestamp": 1375142400000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    },
    {
      "start": {
        "date-parts": [
          [
            2013,
            7,
            30
          ]
        ],
        "date-time": "2013-07-30T00:00:00Z",
        "timestamp": 1375142400000
      },
      "content-version": "am",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    },
    {
      "start": {
        "date-parts": [
          [
            2013,
            7,
            30
          ]
        ],
        "date-time": "2013-07-30T00:00:00Z",
        "timestamp": 1375142400000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    },
    {
      "start": {
        "date-parts": [
          [
            2013,
            7,
            30
          ]
        ],
        "date-time": "2013-07-30T00:00:00Z",
        "timestamp": 1375142400000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    },
    {
      "start": {
        "date-parts": [
          [
            2013,
            7,
            30
          ]
        ],
        "date-time": "2013-07-30T00:00:00Z",
        "timestamp": 1375142400000
      },
      "content-version": "am",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    },
    {
      "start": {
        "date-parts": [
          [
            2013,
            7,
            30
          ]
        ],
        "date-time": "2013-07-30T00:00:00Z",
        "timestamp": 1375142400000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "http://creativecommons.org/licenses/by/3.0/"
    }
  ],
  "funder": [
    {
      "DOI": "10.13039/100000011",
      "name": "Howard Hughes Medical Institute",
      "doi-asserted-by": "crossref",
      "id": [
        {
          "id": "10.13039/100000011",
          "id-type": "DOI",
          "asserted-by": "crossref"
        }
      ]
    },
    {
      "name": "Association Fran\u00e7aise Contre les Myopathies"
    },
    {
      "DOI": "10.13039/100000011",
      "name": "Howard Hughes Medical Institute",
      "doi-asserted-by": "publisher",
      "id": [
        {
          "id": "10.13039/100000011",
          "id-type": "DOI",
          "asserted-by": "publisher"
        }
      ]
    },
    {
      "name": "Association Fran\u00e7aise Contre les Myopathies"
    }
  ],
  "content-domain": {
    "domain": [
      "www.elifesciences.org"
    ],
    "crossmark-restriction": false
  },
  "abstract": "<jats:p>Eukaryotes have two types of spliceosomes, comprised of either major (U1, U2, U4, U5, U6) or minor (U11, U12, U4atac, U6atac; &lt;1%) snRNPs. The high conservation of minor introns, typically one amidst many major introns in several hundred genes, despite their poor splicing, has been a long-standing enigma. Here, we discovered that the low abundance minor spliceosome\u2019s catalytic snRNP, U6atac, is strikingly unstable (t\u00bd&lt;2 hr). We show that U6atac level depends on both RNA polymerases II and III and can be rapidly increased by cell stress-activated kinase p38MAPK, which stabilizes it, enhancing mRNA expression of hundreds of minor intron-containing genes that are otherwise suppressed by limiting U6atac. Furthermore, p38MAPK-dependent U6atac modulation can control minor intron-containing tumor suppressor PTEN expression and cytokine production. We propose that minor introns are embedded molecular switches regulated by U6atac abundance, providing a novel post-transcriptional gene expression mechanism and a rationale for the minor spliceosome\u2019s evolutionary conservation.</jats:p>",
  "DOI": "10.7554/elife.00780",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2013,
        7,
        30
      ]
    ],
    "date-time": "2013-07-30T18:12:58Z",
    "timestamp": 1375207978000
  },
  "source": "Crossref",
  "is-referenced-by-count": 79,
  "title": "Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA",
  "prefix": "10.7554",
  "volume": "2",
  "author": [
    {
      "given": "Ihab",
      "family": "Younis",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United States"
        }
      ]
    },
    {
      "given": "Kimberly",
      "family": "Dittmar",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United States"
        }
      ]
    },
    {
      "given": "Wei",
      "family": "Wang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Computer Science, New Jersey Institute of Technology, Newark, United States"
        }
      ]
    },
    {
      "given": "Shawn W",
      "family": "Foley",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United States"
        }
      ]
    },
    {
      "given": "Michael G",
      "family": "Berg",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United States"
        }
      ]
    },
    {
      "given": "Karen Y",
      "family": "Hu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United States"
        }
      ]
    },
    {
      "given": "Zhi",
      "family": "Wei",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Computer Science, New Jersey Institute of Technology, Newark, United States"
        }
      ]
    },
    {
      "given": "Lili",
      "family": "Wan",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United States"
        }
      ]
    },
    {
      "given": "Gideon",
      "family": "Dreyfuss",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, United States"
        }
      ]
    }
  ],
  "member": "4374",
  "published-online": {
    "date-parts": [
      [
        2013,
        7,
        30
      ]
    ]
  },
  "reference": [
    {
      "key": "bib1",
      "doi-asserted-by": "publisher",
      "first-page": "2885",
      "DOI": "10.1002/ajmg.a.34299",
      "article-title": "A homozygous mutation in RNU4ATAC as a cause of microcephalic osteodysplastic primordial dwarfism type I (MOPD I) with associated pigmentary disorder",
      "volume": "155A",
      "author": "Abdel-Salam",
      "year": "2011",
      "journal-title": "Am J Med Genet A"
    },
    {
      "key": "bib47",
      "doi-asserted-by": "publisher",
      "first-page": "454",
      "DOI": "10.1038/ng.556",
      "article-title": "Subtle variations in Pten dose determine cancer susceptibility",
      "volume": "42",
      "author": "Alimonti",
      "year": "2010",
      "journal-title": "Nat Genet"
    },
    {
      "key": "bib2",
      "doi-asserted-by": "publisher",
      "first-page": "D110",
      "DOI": "10.1093/nar/gkl796",
      "article-title": "U12DB: a database of orthologous U12-type spliceosomal introns",
      "volume": "35",
      "author": "Alioto",
      "year": "2007",
      "journal-title": "Nucleic Acids Res"
    },
    {
      "key": "bib3",
      "doi-asserted-by": "publisher",
      "first-page": "106",
      "DOI": "10.1186/1471-2164-11-106",
      "article-title": "U12 type introns were lost at multiple occasions during evolution",
      "volume": "11",
      "author": "Bartschat",
      "year": "2010",
      "journal-title": "BMC Genomics"
    },
    {
      "key": "bib4",
      "doi-asserted-by": "publisher",
      "first-page": "19",
      "DOI": "10.1186/1745-6150-3-19",
      "article-title": "U12 intron positions are more strongly conserved between animals and plants than U2 intron positions",
      "volume": "3",
      "author": "Basu",
      "year": "2008",
      "journal-title": "Biol Direct"
    },
    {
      "key": "bib5",
      "doi-asserted-by": "publisher",
      "first-page": "53",
      "DOI": "10.1016/j.cell.2012.05.029",
      "article-title": "U1 snRNP determines mRNA length and regulates isoform expression",
      "volume": "150",
      "author": "Berg",
      "year": "2012",
      "journal-title": "Cell"
    },
    {
      "key": "bib6",
      "doi-asserted-by": "publisher",
      "first-page": "815",
      "DOI": "10.1016/S0161-5890(02)00262-6",
      "article-title": "Ribotoxic stress activates p38 and JNK kinases and modulates the antigen-presenting activity of dendritic cells",
      "volume": "39",
      "author": "Bunyard",
      "year": "2003",
      "journal-title": "Mol Immunol"
    },
    {
      "key": "bib7",
      "doi-asserted-by": "publisher",
      "first-page": "773",
      "DOI": "10.1016/S1097-2765(00)80292-0",
      "article-title": "Evolutionary fates and origins of U12-type introns",
      "volume": "2",
      "author": "Burge",
      "year": "1998",
      "journal-title": "Mol Cell"
    },
    {
      "key": "bib8",
      "doi-asserted-by": "publisher",
      "first-page": "164",
      "DOI": "10.1111/j.1365-2567.2006.02347.x",
      "article-title": "Dependence on p38 MAPK signalling in the up-regulation of TLR2, TLR4 and TLR9 gene expression in Trichomonas vaginalis-treated HeLa cells",
      "volume": "118",
      "author": "Chang",
      "year": "2006",
      "journal-title": "Immunology"
    },
    {
      "key": "bib9",
      "doi-asserted-by": "publisher",
      "first-page": "95",
      "DOI": "10.1042/0264-6021:3510095",
      "article-title": "Specificity and mechanism of action of some commonly used protein kinase inhibitors",
      "volume": "351",
      "author": "Davies",
      "year": "2000",
      "journal-title": "Biochem J"
    },
    {
      "key": "bib10",
      "doi-asserted-by": "publisher",
      "first-page": "14",
      "DOI": "10.1016/S0076-6879(06)11002-2",
      "article-title": "Analyzing micro-RNA expression using microarrays",
      "volume": "411",
      "author": "Davison",
      "year": "2006",
      "journal-title": "Methods Enzymol"
    },
    {
      "key": "bib11",
      "doi-asserted-by": "publisher",
      "first-page": "1959",
      "DOI": "10.1261/rna.1136108",
      "article-title": "High-resolution gene expression profiling for simultaneous kinetic parameter analysis of RNA synthesis and decay",
      "volume": "14",
      "author": "Dolken",
      "year": "2008",
      "journal-title": "RNA"
    },
    {
      "key": "bib12",
      "doi-asserted-by": "publisher",
      "first-page": "240",
      "DOI": "10.1126/science.1202205",
      "article-title": "Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA",
      "volume": "332",
      "author": "Edery",
      "year": "2011",
      "journal-title": "Science"
    },
    {
      "key": "bib13",
      "doi-asserted-by": "publisher",
      "first-page": "274",
      "DOI": "10.1093/cvr/cvp425",
      "article-title": "Inactivation of the tumour suppressor, PTEN, in smooth muscle promotes a pro-inflammatory phenotype and enhances neointima formation",
      "volume": "86",
      "author": "Furgeson",
      "year": "2010",
      "journal-title": "Cardiovasc Res"
    },
    {
      "key": "bib14",
      "doi-asserted-by": "crossref",
      "first-page": "5167",
      "DOI": "10.4049/jimmunol.176.9.5167",
      "article-title": "Cutting Edge: Lentiviral short hairpin RNA silencing of PTEN in human mast cells reveals constitutive signals that promote cytokine secretion and cell survival",
      "volume": "176",
      "author": "Furumoto",
      "year": "2006",
      "journal-title": "J Immunol"
    },
    {
      "key": "bib15",
      "doi-asserted-by": "publisher",
      "first-page": "160",
      "DOI": "10.1006/excr.1996.0311",
      "article-title": "U6 snRNA maturation and stability",
      "volume": "228",
      "author": "Fury",
      "year": "1996",
      "journal-title": "Exp Cell Res"
    },
    {
      "key": "bib16",
      "doi-asserted-by": "publisher",
      "first-page": "1716",
      "DOI": "10.1126/science.271.5256.1716",
      "article-title": "Requirement of U12 snRNA for in vivo splicing of a minor class of eukaryotic nuclear pre-mRNA introns",
      "volume": "271",
      "author": "Hall",
      "year": "1996",
      "journal-title": "Science"
    },
    {
      "key": "bib17",
      "doi-asserted-by": "publisher",
      "first-page": "238",
      "DOI": "10.1126/science.1200587",
      "article-title": "Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I",
      "volume": "332",
      "author": "He",
      "year": "2011",
      "journal-title": "Science"
    },
    {
      "key": "bib18",
      "doi-asserted-by": "publisher",
      "first-page": "2185",
      "DOI": "10.1038/sj.emboj.7600212",
      "article-title": "Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125",
      "volume": "23",
      "author": "Heo",
      "year": "2004",
      "journal-title": "EMBO J"
    },
    {
      "key": "bib19",
      "doi-asserted-by": "publisher",
      "first-page": "e2",
      "DOI": "10.1093/nar/gni002",
      "article-title": "Detection and discovery of RNA modifications using microarrays",
      "volume": "33",
      "author": "Hiley",
      "year": "2005",
      "journal-title": "Nucleic Acids Res"
    },
    {
      "key": "bib20",
      "doi-asserted-by": "publisher",
      "first-page": "664",
      "DOI": "10.1038/nature09479",
      "article-title": "U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation",
      "volume": "468",
      "author": "Kaida",
      "year": "2010",
      "journal-title": "Nature"
    },
    {
      "key": "bib21",
      "doi-asserted-by": "publisher",
      "first-page": "1009",
      "DOI": "10.1038/nmeth.1528",
      "article-title": "Analysis and design of RNA sequencing experiments for identifying isoform regulation",
      "volume": "7",
      "author": "Katz",
      "year": "2010",
      "journal-title": "Nat Methods"
    },
    {
      "key": "bib22",
      "doi-asserted-by": "publisher",
      "first-page": "157",
      "DOI": "10.1083/jcb.152.1.157",
      "article-title": "The Telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle",
      "volume": "152",
      "author": "Kickhoefer",
      "year": "2001",
      "journal-title": "J Cell Biol"
    },
    {
      "key": "bib23",
      "doi-asserted-by": "publisher",
      "first-page": "718",
      "DOI": "10.1016/j.cell.2007.09.043",
      "article-title": "Splicing segregation: the minor spliceosome acts outside the nucleus and controls cell proliferation",
      "volume": "131",
      "author": "Konig",
      "year": "2007",
      "journal-title": "Cell"
    },
    {
      "key": "bib24",
      "doi-asserted-by": "publisher",
      "first-page": "e212",
      "DOI": "10.1371/journal.pgen.0030212",
      "article-title": "Extragenic accumulation of RNA polymerase II enhances transcription by RNA polymerase III",
      "volume": "3",
      "author": "Listerman",
      "year": "2007",
      "journal-title": "PLOS Genet"
    },
    {
      "key": "bib25",
      "doi-asserted-by": "publisher",
      "first-page": "621",
      "DOI": "10.1038/nmeth.1226",
      "article-title": "Mapping and quantifying mammalian transcriptomes by RNA-Seq",
      "volume": "5",
      "author": "Mortazavi",
      "year": "2008",
      "journal-title": "Nat Methods"
    },
    {
      "key": "bib26",
      "doi-asserted-by": "publisher",
      "first-page": "439",
      "DOI": "10.1016/S1097-2765(02)00441-0",
      "article-title": "The divergent U12-type spliceosome is required for pre-mRNA splicing and is essential for development in Drosophila",
      "volume": "9",
      "author": "Otake",
      "year": "2002",
      "journal-title": "Mol Cell"
    },
    {
      "key": "bib27",
      "doi-asserted-by": "publisher",
      "first-page": "3804",
      "DOI": "10.1093/emboj/cdf297",
      "article-title": "The splicing of U12-type introns can be a rate-limiting step in gene expression",
      "volume": "21",
      "author": "Patel",
      "year": "2002",
      "journal-title": "EMBO J"
    },
    {
      "key": "bib28",
      "doi-asserted-by": "publisher",
      "first-page": "960",
      "DOI": "10.1038/nrm1259",
      "article-title": "Splicing double: insights from the second spliceosome",
      "volume": "4",
      "author": "Patel",
      "year": "2003",
      "journal-title": "Nat Rev Mol Cell Biol"
    },
    {
      "key": "bib29",
      "doi-asserted-by": "publisher",
      "first-page": "H1806",
      "DOI": "10.1152/ajpheart.00929.2011",
      "article-title": "Regulation of phosphatase and tensin homolog on chromosome 10 in response to hypoxia",
      "volume": "302",
      "author": "Qian",
      "year": "2012",
      "journal-title": "Am J Physiol Heart Circ Physiol"
    },
    {
      "key": "bib30",
      "doi-asserted-by": "publisher",
      "first-page": "841",
      "DOI": "10.1093/bioinformatics/btq033",
      "article-title": "BEDTools: a flexible suite of utilities for comparing genomic features",
      "volume": "26",
      "author": "Quinlan",
      "year": "2010",
      "journal-title": "Bioinformatics"
    },
    {
      "key": "bib31",
      "doi-asserted-by": "publisher",
      "first-page": "863",
      "DOI": "10.1038/nature05228",
      "article-title": "An early evolutionary origin for the minor spliceosome",
      "volume": "443",
      "author": "Russell",
      "year": "2006",
      "journal-title": "Nature"
    },
    {
      "key": "bib32",
      "doi-asserted-by": "publisher",
      "first-page": "1855",
      "DOI": "10.1128/MCB.24.5.1855-1869.2004",
      "article-title": "An intronic enhancer regulates splicing of the twintron of Drosophila melanogaster prospero pre-mRNA by two different spliceosomes",
      "volume": "24",
      "author": "Scamborova",
      "year": "2004",
      "journal-title": "Mol Cell Biol"
    },
    {
      "key": "bib33",
      "doi-asserted-by": "publisher",
      "first-page": "7727",
      "DOI": "10.1074/jbc.M511105200",
      "article-title": "Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) mediates p38 MAPK stress signal-induced inhibition of insulin signaling. A cross-talk between stress signaling and insulin signaling in resistin-treated human endothelial cells",
      "volume": "281",
      "author": "Shen",
      "year": "2006",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "bib34",
      "doi-asserted-by": "publisher",
      "first-page": "3955",
      "DOI": "10.1093/nar/gkl556",
      "article-title": "Comprehensive splice-site analysis using comparative genomics",
      "volume": "34",
      "author": "Sheth",
      "year": "2006",
      "journal-title": "Nucleic Acids Res"
    },
    {
      "key": "bib35",
      "doi-asserted-by": "publisher",
      "first-page": "525",
      "DOI": "10.1017/S1355838299982213",
      "article-title": "Conservation of functional features of U6atac and U12 snRNAs between vertebrates and higher plants",
      "volume": "5",
      "author": "Shukla",
      "year": "1999",
      "journal-title": "RNA"
    },
    {
      "key": "bib36",
      "doi-asserted-by": "publisher",
      "first-page": "1128",
      "DOI": "10.1038/nsmb.1666",
      "article-title": "Rates of in situ transcription and splicing in large human genes",
      "volume": "16",
      "author": "Singh",
      "year": "2009",
      "journal-title": "Nat Struct Mol Biol"
    },
    {
      "key": "bib37",
      "doi-asserted-by": "publisher",
      "first-page": "4071",
      "DOI": "10.1242/jcs.015230",
      "article-title": "New insights into PTEN",
      "volume": "120",
      "author": "Tamguney",
      "year": "2007",
      "journal-title": "J Cell Sci"
    },
    {
      "key": "bib38",
      "doi-asserted-by": "publisher",
      "first-page": "801",
      "DOI": "10.1016/S0092-8674(00)81057-0",
      "article-title": "A novel spliceosome containing U11, U12, and U5 snRNPs excises a minor class (AT-AC) intron in vitro",
      "volume": "84",
      "author": "Tarn",
      "year": "1996",
      "journal-title": "Cell"
    },
    {
      "key": "bib39",
      "doi-asserted-by": "publisher",
      "first-page": "1105",
      "DOI": "10.1093/bioinformatics/btp120",
      "article-title": "TopHat: discovering splice junctions with RNA-Seq",
      "volume": "25",
      "author": "Trapnell",
      "year": "2009",
      "journal-title": "Bioinformatics"
    },
    {
      "key": "bib40",
      "doi-asserted-by": "publisher",
      "first-page": "562",
      "DOI": "10.1038/nprot.2012.016",
      "article-title": "Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks",
      "volume": "7",
      "author": "Trapnell",
      "year": "2012",
      "journal-title": "Nat Protoc"
    },
    {
      "key": "bib41",
      "doi-asserted-by": "publisher",
      "first-page": "511",
      "DOI": "10.1038/nbt.1621",
      "article-title": "Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation",
      "volume": "28",
      "author": "Trapnell",
      "year": "2010",
      "journal-title": "Nat Biotechnol"
    },
    {
      "key": "bib42",
      "doi-asserted-by": "publisher",
      "first-page": "61",
      "DOI": "10.1002/wrna.1141",
      "article-title": "The significant other: splicing by the minor spliceosome",
      "volume": "4",
      "author": "Turunen",
      "year": "2012",
      "journal-title": "Wiley Interdiscip Rev RNA"
    },
    {
      "key": "bib43",
      "doi-asserted-by": "publisher",
      "first-page": "701",
      "DOI": "10.1016/j.cell.2009.02.009",
      "article-title": "The spliceosome: design principles of a dynamic RNP machine",
      "volume": "136",
      "author": "Wahl",
      "year": "2009",
      "journal-title": "Cell"
    },
    {
      "key": "bib44",
      "doi-asserted-by": "publisher",
      "first-page": "551",
      "DOI": "10.1016/j.molcel.2010.03.014",
      "article-title": "Gemin5 delivers snRNA precursors to the SMN complex for snRNP biogenesis",
      "volume": "38",
      "author": "Yong",
      "year": "2010",
      "journal-title": "Mol Cell"
    },
    {
      "key": "bib45",
      "doi-asserted-by": "publisher",
      "first-page": "1718",
      "DOI": "10.1128/MCB.01301-09",
      "article-title": "Rapid-response splicing reporter screens identify differential regulators of constitutive and alternative splicing",
      "volume": "30",
      "author": "Younis",
      "year": "2010",
      "journal-title": "Mol Cell Biol"
    },
    {
      "key": "bib46",
      "doi-asserted-by": "publisher",
      "first-page": "585",
      "DOI": "10.1016/j.cell.2008.03.031",
      "article-title": "SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing",
      "volume": "133",
      "author": "Zhang",
      "year": "2008",
      "journal-title": "Cell"
    }
  ],
  "container-title": "eLife",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://cdn.elifesciences.org/articles/00780/elife-00780-v1.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://cdn.elifesciences.org/articles/00780/elife-00780-v1.xml",
      "content-type": "application/xml",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://elifesciences.org/articles/00780",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        10,
        12
      ]
    ],
    "date-time": "2023-10-12T00:40:30Z",
    "timestamp": 1697071230000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://elifesciences.org/articles/00780"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2013,
        7,
        30
      ]
    ]
  },
  "references-count": 47,
  "alternative-id": [
    "10.7554/eLife.00780"
  ],
  "URL": "http://dx.doi.org/10.7554/eLife.00780",
  "relation": {
    "is-supplemented-by": [
      {
        "id-type": "accession",
        "id": "GSE48263",
        "asserted-by": "subject"
      }
    ],
    "has-review": [
      {
        "id-type": "doi",
        "id": "10.7554/eLife.00780.016",
        "asserted-by": "object"
      },
      {
        "id-type": "doi",
        "id": "10.7554/eLife.00780.017",
        "asserted-by": "object"
      }
    ]
  },
  "ISSN": [
    "2050-084X"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2013,
        7,
        30
      ]
    ]
  },
  "assertion": [
    {
      "value": "2013-03-27",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2013-06-27",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2013-07-30",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ],
  "article-number": "e00780"
}