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PMID: 16227573 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells.

Molecular and cellular biology ·Vol. 25 ·No. 21 ·2005-11-00 ·Pages 9198-208

Wu L, Belasco JG

Abstract

Vertebrate genomes each encode hundreds of micro-RNAs (miRNAs), yet for few of these miRNAs is there empirical evidence as to which mRNA(s) they regulate. Here we report the identification of human lin-28 mRNA as a regulatory target of human miR-125b and its homolog miR-125a. Studies of miR-125b function in mouse P19 embryonal carcinoma cells induced to develop into neurons suggest a role for this regulatory miRNA in mammalian neuronal differentiation, since its increased concentration in these cells contributes to lin-28 downregulation. Within the lin-28 3' untranslated region (UTR) are two conserved miRNA responsive elements (miREs) that mediate repression by miR-125b and miR-125a. Simultaneous deletion of both miREs renders the lin-28 3' UTR almost completely insensitive to these miRNAs, indicating that these two miREs are the principal elements in the lin-28 3' UTR that respond to miR-125. At the 3' end of each element is an adenosine residue that makes a significant contribution to function irrespective of its complementarity to the 5'-terminal nucleotide of miR-125. By contrast to most earlier reports of gene repression by other miRNAs that are imperfectly complementary to their targets, lin-28 downregulation by miR-125 involves reductions in both translational efficiency and mRNA abundance. The decrease in the mRNA concentration is achieved by a posttranscriptional mechanism that is independent of the inhibitory effect on translation.

MeSH Terms
3' Untranslated Regions/metabolism Animals Cell Differentiation/physiology Cell Line Down-Regulation Embryonal Carcinoma Stem Cells Genes, Reporter Humans Mice MicroRNAs/metabolism Neoplastic Stem Cells/cytology,metabolism Neurons/cytology,metabolism RNA, Messenger/metabolism RNA-Binding Proteins/genetics,metabolism
Chemicals
3' Untranslated Regions MicroRNAs RNA, Messenger RNA-Binding Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wu Ligang
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Belasco Joel G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.21.9198-9208.2005
Published
2005-11-00
Pages
9198-208
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1265813
Subset
IM
Grants
NIGMS NIH HHS · R01 GM055624 · United States
NIGMS NIH HHS · GM 55624 · United States
External Links
PubMed source DOI: 10.1128/MCB.25.21.9198-9208.2005 PMC Full Text View journal details
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