Open AccessMicro-RNA Regulation of the Mammalian lin-28 Gene during Neuronal Differentiation of Embryonal Carcinoma Cells
Author(s) -
Ligang Wu,
Joel G. Belasco
Publication year - 2005
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.25.21.9198-9208.2005
Subject(s) - biology , psychological repression , microrna , au rich element , three prime untranslated region , untranslated region , messenger rna , downregulation and upregulation , regulation of gene expression , gene , gene expression , genetics , microbiology and biotechnology , translational regulation , translation (biology)
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 humanlin-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 tolin-28 downregulation. Within thelin-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 thelin-28 3′ UTR almost completely insensitive to these miRNAs, indicating that these two miREs are the principal elements in thelin-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.