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

PLoS One. 2008 Jul 2;3(7):e2548. doi: 10.1371/journal.pone.0002548.

Abstract

Background: 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).

Methodology/principal findings: 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.

Conclusion/significance: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Blotting, Northern / methods
  • Cell Differentiation
  • Computational Biology / methods
  • Conserved Sequence
  • Embryonic Stem Cells / cytology*
  • False Positive Reactions
  • Humans
  • MicroRNAs / metabolism*
  • Models, Biological
  • Models, Genetic
  • RNA, Messenger / metabolism*
  • Time Factors
  • Tretinoin / metabolism

Substances

  • MicroRNAs
  • RNA, Messenger
  • Tretinoin