DOI: 10.1126/science.1090599. Nuclear Export of MicroRNA Precursors

10.1126/science.1090599

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III–like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate–dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro. Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.

Bibliography

Lund, E., GuÌttinger, S., Calado, A., Dahlberg, J. E., & Kutay, U. (2004). Nuclear Export of MicroRNA Precursors. Science, 303(5654), 95â98.

Authors 5

Elsebet Lund (first)
Stephan Güttinger (additional)
Angelo Calado (additional)
James E. Dahlberg (additional)
Ulrike Kutay (additional)

References 31 Referenced 2,027

10.1126/science.1064921
10.1126/science.1065062
10.1126/science.1065329
10.1101/gad.974702
10.1101/gad.1004402
10.1101/gad.1026102
10.1016/S0960-9822(02)01206-X
10.1038/nrm1129
10.1016/0092-8674(93)90529-Y
10.1002/bies.10046
10.1146/annurev.cellbio.18.012502.105832
10.1126/science.1085242
10.1016/S0168-9525(02)00011-2
10.1093/emboj/cdf476
10.1038/nature01957
10.1126/science.1062961
10.1101/gad.927801
10.1261/rna.2780503
Materials and Methods are available as supporting material on Science Online.
10.1093/emboj/cdf582
10.1007/s00018-003-3070-3
10.1093/emboj/16.21.6535
E. Lund et al . unpublished data.
10.1083/jcb.200110082
10.1074/jbc.C200668200
10.1093/emboj/cdf620
M. Terns, E. Lund, J. Dahlberg, Mol. Cell Biol.12, 3032 (1992). / Mol. Cell Biol. (1992)
10.1093/emboj/16.4.793
10.1093/emboj/cdf613
10.1242/dev.00362
We thank E. White and B. Clark for technical assistance; M. Olson H. Allawi V. Lyamichev and S. Olson of Third Wave Technologies Inc. Madison WI for help with Invader assays; C. B. Jensen for initiating in vitro Dicer experiments; and G. Lipowsky and S. Hasan for critically reading the manuscript. UK is supported by the Swiss National Science Foundation and J.E.D. and E.L. are supported by NIH grant GM-30220. J.E.D and E.L. have a financial interest in Third Wave Technologies Inc.

Dates

Type	When
Created	21 years, 9 months ago (Nov. 24, 2003, 8:16 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 9:48 p.m.)
Indexed	21 hours, 59 minutes ago (Aug. 27, 2025, noon)
Issued	21 years, 7 months ago (Jan. 2, 2004)
Published	21 years, 7 months ago (Jan. 2, 2004)
Published Print	21 years, 7 months ago (Jan. 2, 2004)

Funders 0

None

BibTeX

@article{Lund_2004, title={Nuclear Export of MicroRNA Precursors}, volume={303}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1090599}, DOI={10.1126/science.1090599}, number={5654}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Lund, Elsebet and Güttinger, Stephan and Calado, Angelo and Dahlberg, James E. and Kutay, Ulrike}, year={2004}, month=jan, pages={95–98} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        27
      ]
    ],
    "date-time": "2025-08-27T16:00:49Z",
    "timestamp": 1756310449384
  },
  "reference-count": 31,
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "issue": "5654",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2004,
        1,
        2
      ]
    ]
  },
  "abstract": "<jats:p>MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III\u2013like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate\u2013dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro. Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.</jats:p>",
  "DOI": "10.1126/science.1090599",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2003,
        11,
        25
      ]
    ],
    "date-time": "2003-11-25T01:16:09Z",
    "timestamp": 1069722969000
  },
  "page": "95-98",
  "source": "Crossref",
  "is-referenced-by-count": 2027,
  "title": "Nuclear Export of MicroRNA Precursors",
  "prefix": "10.1126",
  "volume": "303",
  "author": [
    {
      "given": "Elsebet",
      "family": "Lund",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA."
        },
        {
          "name": "Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich CH-8093, Switzerland."
        }
      ]
    },
    {
      "given": "Stephan",
      "family": "Gu\u0308ttinger",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA."
        },
        {
          "name": "Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich CH-8093, Switzerland."
        }
      ]
    },
    {
      "given": "Angelo",
      "family": "Calado",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA."
        },
        {
          "name": "Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich CH-8093, Switzerland."
        }
      ]
    },
    {
      "given": "James E.",
      "family": "Dahlberg",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA."
        },
        {
          "name": "Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich CH-8093, Switzerland."
        }
      ]
    },
    {
      "given": "Ulrike",
      "family": "Kutay",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA."
        },
        {
          "name": "Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich CH-8093, Switzerland."
        }
      ]
    }
  ],
  "member": "221",
  "reference": [
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1064921"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1065062"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1065329"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.974702"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.1004402"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.1026102"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0960-9822(02)01206-X"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrm1129"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(93)90529-Y"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/bies.10046"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.cellbio.18.012502.105832"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1085242"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0168-9525(02)00011-2"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/cdf476"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature01957"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1062961"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.927801"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1261/rna.2780503"
    },
    {
      "key": "e_1_3_2_20_2",
      "unstructured": "Materials and Methods are available as supporting material on Science Online."
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/cdf582"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/s00018-003-3070-3"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/16.21.6535"
    },
    {
      "key": "e_1_3_2_24_2",
      "unstructured": "E. Lund et al . unpublished data."
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200110082"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.C200668200"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/cdf620"
    },
    {
      "key": "e_1_3_2_28_2",
      "first-page": "3032",
      "volume": "12",
      "year": "1992",
      "unstructured": "M. Terns, E. Lund, J. Dahlberg, Mol. Cell Biol.12, 3032 (1992).",
      "journal-title": "Mol. Cell Biol."
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/16.4.793"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/cdf613"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/dev.00362"
    },
    {
      "key": "e_1_3_2_32_2",
      "unstructured": "We thank E. White and B. Clark for technical assistance; M. Olson H. Allawi V. Lyamichev and S. Olson of Third Wave Technologies Inc. Madison WI for help with Invader assays; C. B. Jensen for initiating in vitro Dicer experiments; and G. Lipowsky and S. Hasan for critically reading the manuscript. UK is supported by the Swiss National Science Foundation and J.E.D. and E.L. are supported by NIH grant GM-30220. J.E.D and E.L. have a financial interest in Third Wave Technologies Inc."
    }
  ],
  "container-title": "Science",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.science.org/doi/pdf/10.1126/science.1090599",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        10
      ]
    ],
    "date-time": "2024-01-10T02:48:46Z",
    "timestamp": 1704854926000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.science.org/doi/10.1126/science.1090599"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2004,
        1,
        2
      ]
    ]
  },
  "references-count": 31,
  "journal-issue": {
    "issue": "5654",
    "published-print": {
      "date-parts": [
        [
          2004,
          1,
          2
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.1090599"
  ],
  "URL": "http://dx.doi.org/10.1126/science.1090599",
  "relation": {
    "has-review": [
      {
        "id-type": "doi",
        "id": "10.3410/f.1016804.201691",
        "asserted-by": "object"
      },
      {
        "id-type": "doi",
        "id": "10.3410/f.1016804.235443",
        "asserted-by": "object"
      },
      {
        "id-type": "doi",
        "id": "10.3410/f.1016804.201434",
        "asserted-by": "object"
      }
    ]
  },
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        2004,
        1,
        2
      ]
    ]
  }
}