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Mechanisms and reversibility of miRNA‐mediated translational repression and P‐body localization of human mRNAs
Author(s) -
Filipowicz Witold
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a149-d
Subject(s) - psychological repression , polysome , translation (biology) , derepression , p bodies , microrna , messenger rna , translational regulation , untranslated region , microbiology and biotechnology , three prime untranslated region , biology , protein biosynthesis , au rich element , gene expression , chemistry , rna , gene , genetics , ribosome
MiRNAs regulate gene expression post‐transcriptionally, by imperfectly base‐pairing to 3′UTR of mRNAs, what results in translational repression or mRNA degradation. Studies carried out in HeLa and hepatoma cells, using reporters, and also endogenous mRNAs such as the mRNA encoding the cationic amino acid transporter (CAT‐1), indicated that miRNAs let‐7 and miR‐122 primarily repress translation at the initiation step. Repressed mRNAs are re‐localized to P‐bodies, cellular structures involved in storage and degradation of mRNAs. Our results support a two‐step mechanism of miRNA action, with the localization to P‐bodies being a secondary event, following inhibition of translation. Examples of specific mRNAs undergoing miRNA‐mediated repression are numerous but whether the repression is a reversible process remains largely unknown. Under conditions of cellular stress the repressed CAT‐1 mRNA or reporters bearing its 3′UTR exit P‐bodies to reassociate with polysomes and to reenter translation. The derepression requires binding of HuR, an AU‐rich‐element‐binding protein, to CAT‐1 mRNA 3′UTR. Our data provide evidence that P‐bodies function in storage of miRNA‐repressed mRNAs and demonstrate that miRNA‐mediated repression is a reversible process.