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

• Published in: PloS one Vol. 3; no. 7; p. e2548
• Main Authors: Gu, Peili, Reid, Jeffrey G, Gao, Xiaolian, Shaw, Chad A, Creighton, Chad, Tran, Peter L, Zhou, Xiaochuan, 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.07.2008; Public Library of Science (PLoS)
• Subjects: Algorithms; Animals; Biochemistry; Bioinformatics; Blotting, Northern - methods; Caenorhabditis elegans; Cancer; Cell cycle; Cell Differentiation; Cell self-renewal; Cellular biology; Computational Biology - methods; Conserved Sequence; Differentiation (biology); Drosophila; Embryonic Stem Cells - cytology; False Positive Reactions; Gene expression; Gene regulation; Gene silencing; Genetics and Genomics; Genetics and Genomics/Bioinformatics; Genetics and Genomics/Gene Discovery; Genetics and Genomics/Gene Expression; Genetics and Genomics/Genomics; Genomes; Humans; Insects; Mammals; Medicine; MicroRNAs; MicroRNAs - metabolism; miRNA; Models, Biological; Models, Genetic; Perturbation; Physicians; Pluripotency; Retinoic acid; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Stem cells; Target recognition; Time Factors; Tissues; Transcription; Trends; Tretinoin - metabolism; Tribolium; Tribolium castaneum; User interface; United States > US; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0002548

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.