{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:35:52Z","timestamp":1773290152032,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2004,9,28]],"date-time":"2004-09-28T00:00:00Z","timestamp":1096329600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"},{"start":{"date-parts":[[2004,9,28]],"date-time":"2004-09-28T00:00:00Z","timestamp":1096329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>MicroRNAs are ~17\u201324 nt. noncoding RNAs found in all eukaryotes that degrade messenger RNAs via RNA interference (if they bind in a perfect or near-perfect complementarity to the target mRNA), or arrest translation (if the binding is imperfect). Several microRNA targets have been identified in lower organisms, but only one mammalian microRNA target has yet been validated experimentally.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>We carried out a population-wide statistical analysis of how human microRNAs interact complementarily with human mRNAs, looking for characteristics that differ significantly as compared with scrambled control sequences. These characteristics were used to identify a set of 71 outlier mRNAs unlikely to have been hit by chance.<\/jats:p>\n                        <jats:p>Unlike the case in <jats:italic>C. elegans<\/jats:italic> and <jats:italic>Drosophila<\/jats:italic>, many human microRNAs exhibited long exact matches (10 or more bases in a row), up to and including perfect target complementarity. Human microRNAs hit outlier mRNAs within the protein coding region about 2\/3 of the time. And, the stretches of perfect complementarity within microRNA hits onto outlier mRNAs were not biased near the 5'-end of the microRNA. In several cases, an individual microRNA hit multiple mRNAs that belonged to the same functional class.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>The analysis supports the notion that sequence complementarity is the basis by which microRNAs recognize their biological targets, but raises the possibility that human microRNA-mRNA target interactions follow different rules than have been previously characterized in <jats:italic>Drosophila<\/jats:italic> and <jats:italic>C. elegans<\/jats:italic>.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1471-2105-5-139","type":"journal-article","created":{"date-parts":[[2004,10,1]],"date-time":"2004-10-01T06:23:29Z","timestamp":1096611809000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A population-based statistical approach identifies parameters characteristic of human microRNA-mRNA interactions"],"prefix":"10.1186","volume":"5","author":[{"given":"Neil R","family":"Smalheiser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vetle I","family":"Torvik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2004,9,28]]},"reference":[{"key":"255_CR1","doi-asserted-by":"publisher","first-page":"R925","DOI":"10.1016\/j.cub.2003.11.017","volume":"13","author":"EC Lai","year":"2003","unstructured":"Lai EC: microRNAs: runts of the genome assert themselves.\n                           Curr Biol 2003, 13: R925\u2013936. 10.1016\/j.cub.2003.11.017","journal-title":"Curr Biol"},{"key":"255_CR2","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1126\/science.1085242","volume":"301","author":"JC Carrington","year":"2003","unstructured":"Carrington JC, Ambros V: Role of microRNAs in plant and animal development.\n                           Science 2003, 301: 336\u2013338. 10.1126\/science.1085242","journal-title":"Science"},{"key":"255_CR3","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1261\/rna.5181104","volume":"10","author":"PT Nelson","year":"2004","unstructured":"Nelson PT, Hatzigeorgiou AG, Mourelatos Z: miRNP:mRNA association in polyribosomes in a human neuronal cell line.\n                           RNA 2004, 10: 387\u2013394. 10.1261\/rna.5181104","journal-title":"RNA"},{"key":"255_CR4","doi-asserted-by":"publisher","first-page":"R13","DOI":"10.1186\/gb-2004-5-3-r13","volume":"5","author":"LF Sempere","year":"2004","unstructured":"Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V: Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation.\n                           Genome Biol 2004, 5: R13. 10.1186\/gb-2004-5-3-r13","journal-title":"Genome Biol"},{"key":"255_CR5","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1186\/gb-2003-5-1-r1","volume":"5","author":"AJ Enright","year":"2003","unstructured":"Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS: MicroRNA targets in Drosophila.\n                           Genome Biol 2003, 5: R1. 10.1186\/gb-2003-5-1-r1","journal-title":"Genome Biol"},{"key":"255_CR6","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1371\/journal.pbio.0000060","volume":"1","author":"A Stark","year":"2003","unstructured":"Stark A, Brennecke J, Russell RB, Cohen SM: Identification of Drosophila MicroRNA Targets.\n                           PLOS Biol 2003, 1: 397\u2013409. 10.1371\/journal.pbio.0000060","journal-title":"PLOS Biol"},{"key":"255_CR7","doi-asserted-by":"crossref","unstructured":"Rajewsky N, Socci ND: Computational identification of microRNA targets.\n                           Dev Biol\n                           267: 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