DOI: 10.1101/gad.819900. Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in <i>C. elegans</i>

Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans

10.1101/gad.819900

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

Messenger RNA surveillance, the selective and rapid degradation of mRNAs containing premature stop codons, occurs in all eukaryotes tested. The biological role of this decay pathway, however, is not well understood. To identify natural substrates of mRNA surveillance, we used a cDNA-based representational difference analysis to identify mRNAs whose abundance increases in Caenorhabditis elegans smg(−) mutants, which are deficient for mRNA surveillance. Alternatively spliced mRNAs of genes encoding ribosomal proteins L3, L7a, L10a, and L12 are abundant natural targets of mRNA surveillance. Each of these genes expresses two distinct mRNAs. A productively spliced mRNA, whose abundance does not change in smg(−)mutants, encodes a normal, full-length, ribosomal protein. An unproductively spliced mRNA, whose abundance increases dramatically insmg(−) mutants, contains premature stop codons because of incomplete removal of an alternatively spliced intron. In transgenic animals expressing elevated quantities of RPL-12, a greater proportion of endogenous rpl-12 transcript is spliced unproductively. Thus, RPL-12 appears to autoregulate its own splicing, with unproductively spliced mRNAs being degraded by mRNA surveillance. We demonstrate further that alternative splicing of rpl introns is conserved among widely diverged nematodes. Our results suggest that one important role of mRNA surveillance is to eliminate unproductive by-products of gene regulation.

Bibliography

Mitrovich, Q. M., & Anderson, P. (2000). Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans. Genes & Development, 14(17), 2173â2184.

Authors 2

Quinn M. Mitrovich (first)
Philip Anderson (additional)

References 49 Referenced 162

10.1126/science.282.5396.2012
10.1016/0022-2836(92)90545-U
10.1002/j.1460-2075.1985.tb03636.x / EMBO J. / Consequences of frameshift mutations at the immunoglobulin heavy chain locus of the mouse. by Baumann (1985)
10.1016/0092-8674(90)90723-R
10.1038/32160
Blumenthal T. Steward K. (1997) RNA processing and gene structure. in C. elegans II, eds Riddle D.L. Blumenthal T. Meyer B.J. Priess J.R. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York), pp 117–145.
10.1007/s004380050883
10.1093/genetics/151.2.605 / Genetics / smg-7 is required for mRNA surveillance in C. elegans. by Cali (1999)
10.1074/jbc.270.48.28995
10.1073/pnas.81.7.1991
10.1002/(SICI)1521-1878(199908)21:8<685::AID-BIES8>3.0.CO;2-4
{'key': '2021111419230340000_14.17.2173.12', 'first-page': '346', 'article-title': '18S ribosomal RNA gene phylogeny for some Rhabditidae related to Caenorhabditis.', 'volume': '12', 'author': 'Fitch', 'year': '1995', 'journal-title': 'Mol. Biol. Evol.'} / Mol. Biol. Evol. / 18S ribosomal RNA gene phylogeny for some Rhabditidae related to Caenorhabditis. by Fitch (1995)
Fitch D.H.A. Thomas W.K. (1997) Evolution. in C. elegans II, eds Riddle D.L. Blumenthal T. Meyer B.J. Priess J.R. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York), pp 815–850.
10.1016/0076-6879(87)52038-9 / Methods Enzymol. / Second-strand cDNA synthesis: mRNA fragments as primers. by Gubler (1987)
10.1073/pnas.90.15.7034
10.1093/bioinformatics/5.2.151
10.1146/annurev.genet.33.1.229
10.1093/genetics/123.2.301 / Genetics / A new kind of informational suppression in the nematode Caenorhabditis elegans. by Hodgkin (1989)
10.1093/nar/22.25.5640
10.1093/emboj/16.16.5077
10.1093/nar/28.1.91
10.1016/0092-8674(93)90113-5
{'key': '2021111419230340000_14.17.2173.23', 'first-page': '2081', 'article-title': 'The Caenorhabditis elegans rol-6 gene, which interacts with the sqt-1 collagen gene to determine organismal morphology, encodes a collagen.', 'volume': '10', 'author': 'Kramer', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The Caenorhabditis elegans rol-6 gene, which interacts with the sqt-1 collagen gene to determine organismal morphology, encodes a collagen. by Kramer (1990)
10.1016/0092-8674(93)90529-Y
{'key': '2021111419230340000_14.17.2173.25', 'first-page': '2165', 'article-title': 'Gene products that promote mRNA turnover in Saccharomyces cerevisiae.', 'volume': '12', 'author': 'Leeds', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Gene products that promote mRNA turnover in Saccharomyces cerevisiae. by Leeds (1992)
10.1128/MCB.19.10.6710 / Mol. Cell. Biol. / Yeast Upf proteins required for RNA surveillance affect global expression of the yeast transcriptome. by Lelivelt (1999)
10.1016/S0091-679X(08)61381-3
10.1128/MCB.15.11.6454 / Mol. Cell. Biol. / Feedback inhibition of the yeast ribosomal protein gene CRY2 is mediated by the nucleotide sequence and secondary structure of CRY2 pre-mRNA. by Li (1995)
10.1016/0076-6879(95)54021-0
10.1006/jmbi.1999.2700
10.1146/annurev.biochem.64.1.897
10.1016/S0091-679X(08)61399-0
10.1128/MCB.18.5.2932 / Mol. Cell. Biol. / Selenium deficiency reduces the abundance of mRNA for Se-dependent glutathione peroxidase 1 by a UGA-dependent mechanism likely to be nonsense codon-mediated decay of cytoplasmic mRNA. by Moriarty (1998)
10.1073/pnas.94.18.9782
10.1093/bioinformatics/4.1.11
10.1146/annurev.bi.53.070184.000451
10.1128/MCB.19.9.5943 / Mol. Cell. Biol. / SMG-2 is a phosphorylated protein required for mRNA surveillance in Caenorhabditis elegans and related to Upf1p of yeast. by Page (1999)
10.1073/pnas.93.20.10928
10.1101/gad.7.10.1885
10.1016/S0378-1119(96)00519-7
{'key': '2021111419230340000_14.17.2173.41', 'first-page': '23', 'article-title': 'An alternative method for the visualization of RNA in formaldehyde agarose gels.', 'volume': '12', 'author': 'Rosen', 'year': '1990', 'journal-title': 'Focus'} / Focus / An alternative method for the visualization of RNA in formaldehyde agarose gels. by Rosen (1990)
Sambrook J. Fritsch E.F. Maniatis T. (1989) Molecular cloning. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York).
10.1093/nar/15.11.4403
10.1073/pnas.95.17.10009
10.1016/S0955-0674(99)80050-7
10.1074/jbc.272.6.3302
10.1007/BF00292335
10.1101/gad.8.2.211
10.1093/emboj/18.21.6134

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 8 p.m.)
Deposited	3 years, 9 months ago (Nov. 14, 2021, 10:35 p.m.)
Indexed	1 month, 3 weeks ago (July 11, 2025, 6:45 a.m.)
Issued	25 years ago (Sept. 1, 2000)
Published	25 years ago (Sept. 1, 2000)
Published Online	25 years ago (Sept. 1, 2000)
Published Print	25 years ago (Sept. 1, 2000)

Funders 0

None

BibTeX

@article{Mitrovich_2000, title={Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans}, volume={14}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.819900}, DOI={10.1101/gad.819900}, number={17}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Mitrovich, Quinn M. and Anderson, Philip}, year={2000}, month=sep, pages={2173–2184} }

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  "alternative-id": [
    "10.1101/gad.819900"
  ],
  "URL": "http://dx.doi.org/10.1101/gad.819900",
  "relation": {},
  "ISSN": [
    "0890-9369",
    "1549-5477"
  ],
  "subject": [],
  "container-title-short": "Genes Dev.",
  "published": {
    "date-parts": [
      [
        2000,
        9,
        1
      ]
    ]
  }
}