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

TitleNovel microRNA candidates and miRNA-mRNA pairs in embryonic stem (ES) cells.
Publication TypeJournal Article
Year of Publication2008
AuthorsGu, P, Reid, JG, Gao, X, Shaw, CA, Creighton, C, Tran, PL, Zhou, X, Drabek, RB, Steffen, DL, Hoang, DM, Weiss, MK, Naghavi, AO, El-daye, J, Khan, MF, Legge, GB, Wheeler, DA, Gibbs, RA, Miller, JN, Cooney, AJ, Gunaratne, PH
JournalPLoS One
Volume3
Issue7
Paginatione2548
Date Published2008 Jul 02
ISSN1932-6203
KeywordsAlgorithms, Animals, Blotting, Northern, Cell Differentiation, Computational Biology, Conserved Sequence, Embryonic Stem Cells, False Positive Reactions, Humans, MicroRNAs, Models, Biological, Models, Genetic, RNA, Messenger, Time Factors, Tretinoin
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.

DOI10.1371/journal.pone.0002548
Alternate JournalPLoS ONE
PubMed ID18648548
PubMed Central IDPMC2481296
Grant ListU54 HG003273 / HG / NHGRI NIH HHS / United States
2 U54 HG003273-04 / HG / NHGRI NIH HHS / United States
NIDDK 73524 / / PHS HHS / United States
RFA-DK-02-027 / DK / NIDDK NIH HHS / United States