Novel microRNA candidates and miRNA-mRNA pairs in embryonic stem (ES) cells.
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.
Gu
Peili
P
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Reid
Jeffrey G
JG
Gao
Xiaolian
X
Shaw
Chad A
CA
Creighton
Chad
C
Tran
Peter L
PL
Zhou
Xiaochuan
X
Drabek
Rafal B
RB
Steffen
David L
DL
Hoang
David M
DM
Weiss
Michelle K
MK
Naghavi
Arash O
AO
El-daye
Jad
J
Khan
Mahjabeen F
MF
Legge
Glen B
GB
Wheeler
David A
DA
Gibbs
Richard A
RA
Miller
Jonathan N
JN
Cooney
Austin J
AJ
Gunaratne
Preethi H
PH
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
D035683:MicroRNAs; D012333:RNA, Messenger; D014212:Tretinoin