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Evidence for the biogenesis of more than 1,000 novel human microRNAs

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  • Marc R Friedländer
  • Esther Lizano
  • Anna Js Houben
  • Daniela Bezdan
  • Mónica Báñez-Coronel
  • Grzegorz Kudla
  • Elisabet Mateu-Huertas
  • Birgit Kagerbauer
  • Justo González
  • Kevin C Chen
  • Emily M Leproust
  • Eulàlia Martí
  • Xavier Estivill

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    Rights statement: © 2014 Friedländer et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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http://genomebiology.com/2014/15/4/R57
Original languageEnglish
Pages (from-to)R57
JournalGenome Biology
Volume15
Issue number4
DOIs
Publication statusPublished - 7 Apr 2014

Abstract

BACKGROUND: MicroRNAs (miRNAs) are established regulators of development, cell identity and disease. Although nearly two thousand human miRNA genes are known and new ones are continuously discovered, no attempt has been made to gauge the total miRNA content of the human genome.

RESULTS: Employing an innovative computational method on massively pooled small RNA sequencing data, we report 2,469 novel human miRNA candidates of which 1,098 are validated by in-house and published experiments. Almost 300 candidates are robustly expressed in a neuronal cell system and are regulated during differentiation or when biogenesis factors Dicer, Drosha, DGCR8 or Ago2 are silenced. To improve expression profiling we devised a quantitative miRNA capture system. In a kidney cell system 400 candidates interact with DGCR8 at transcript positions that suggest miRNA hairpin recognition, and 1,000 of the new miRNA candidates interact with Ago1 or Ago2, indicating that they are directly bound by miRNA effector proteins. From kidney cell CLASH experiments, in which miRNA-target pairs are ligated and sequenced, we observe hundreds of interactions between novel miRNAs and mRNA targets. The novel miRNA candidates are specifically but lowly expressed, raising the possibility that not all may be functional. Interestingly, the majority are evolutionarily young and overrepresented in the human brain.

CONCLUSIONS: In summary, we present evidence that the complement of human miRNA genes is substantially larger than anticipated, and that more are likely to be discovered in the future as more tissues and experimental conditions are sequenced to greater depth.

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