PLoS ONE (Jul 2008)

Novel microRNA candidates and miRNA-mRNA pairs in embryonic stem (ES) cells.

  • Peili Gu,
  • Jeffrey G Reid,
  • Xiaolian Gao,
  • Chad A Shaw,
  • Chad Creighton,
  • Peter L Tran,
  • Xiaochuan Zhou,
  • Rafal B Drabek,
  • David L Steffen,
  • David M Hoang,
  • Michelle K Weiss,
  • Arash O Naghavi,
  • Jad El-daye,
  • Mahjabeen F Khan,
  • Glen B Legge,
  • David A Wheeler,
  • Richard A Gibbs,
  • Jonathan N Miller,
  • Austin J Cooney,
  • Preethi H Gunaratne

DOI
https://doi.org/10.1371/journal.pone.0002548
Journal volume & issue
Vol. 3, no. 7
p. e2548

Abstract

Read online

MicroRNAS (miRNAS: a class of short non-coding RNAs) are emerging as important agents of post transcriptional gene regulation and integral components of gene networks. MiRNAs have been strongly linked to stem cells, which have a remarkable dual role in development. They can either continuously replenish themselves (self-renewal), or differentiate into cells that execute a limited number of specific actions (pluripotence).In order to identify novel miRNAs from narrow windows of development we carried out an in silico search for micro-conserved elements (MCE) in adult tissue progenitor transcript sequences. A plethora of previously unknown miRNA candidates were revealed including 545 small RNAs that are enriched in embryonic stem (ES) cells over adult cells. Approximately 20% of these novel candidates are down-regulated in ES (Dicer(-/-)) ES cells that are impaired in miRNA maturation. The ES-enriched miRNA candidates exhibit distinct and opposite expression trends from mmu-mirs (an abundant class in adult tissues) during retinoic acid (RA)-induced ES cell differentiation. Significant perturbation of trends is found in both miRNAs and novel candidates in ES (GCNF(-/-)) cells, which display loss of repression of pluripotence genes upon differentiation.Combining expression profile information with miRNA target prediction, we identified miRNA-mRNA pairs that correlate with ES cell pluripotence and differentiation. Perturbation of these pairs in the ES (GCNF(-/-)) mutant suggests a role for miRNAs in the core regulatory networks underlying ES cell self-renewal, pluripotence and differentiation.