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- Title
Novel MicroRNA Candidates and miRNA-mRNA Pairs in Embryonic Stem (ES) Cells.
- Authors
Gu, Peili; Reid, Jeffrey G.; Gao, Xiaolian; Shaw, Chad A.; Creighton, Chad; Tran, Peter L.; Xiaochuan Zhou; Drabek, Rafal B.; Steffen, David L.; Hoang, David M.; Weiss, Michelle K.; Naghavi, Arash O.; El-daye, Jad; Khan, Mahjabeen F.; Legge, Glen B.; Wheeler, David A.; Gibbs, Richard A.; Miller, Jonathan N.; Cooney, Austin J.; Gunaratne, Preethi H.
- 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 miRNAmRNA 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.
- Subjects
EMBRYONIC stem cell research; RNA; RIBOSOMAL DNA; MESSENGER RNA; GENETIC regulation; GENE expression; TRETINOIN; CELL differentiation; GENES
- Publication
PLoS ONE, 2008, Vol 3, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0002548