title: Novel microRNA candidates and miRNA-mRNA pairs in embryonic stem (ES) cells.
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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Peili
authors.initials: P
authors.lastname: Gu
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Reid
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Gao
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.forename: Chad
authors.initials: C
authors.lastname: Creighton
authors.forename: Peter L
authors.initials: PL
authors.lastname: Tran
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Rafal B
authors.initials: RB
authors.lastname: Drabek
authors.forename: David L
authors.initials: DL
authors.lastname: Steffen
authors.forename: David M
authors.initials: DM
authors.lastname: Hoang
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Weiss
authors.forename: Arash O
authors.initials: AO
authors.lastname: Naghavi
authors.forename: Jad
authors.initials: J
authors.lastname: El-daye
authors.forename: Mahjabeen F
authors.initials: MF
authors.lastname: Khan
authors.forename: Glen B
authors.initials: GB
authors.lastname: Legge
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Miller
authors.forename: Austin J
authors.initials: AJ
authors.lastname: Cooney
authors.forename: Preethi H
authors.initials: PH
authors.lastname: Gunaratne
mesh_terms: D000465:Algorithms; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D002454:Cell Differentiation; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D053595:Embryonic Stem Cells / Q000166:cytology*; D005189:False Positive Reactions; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D008957:Models, Genetic; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D014212:Tretinoin