Stress-induced reversal of microRNA repression and mRNA P-body localization in human cells.

Abstract

In metazoa, microRNAs (miRNAs) imperfectly base-pair with the 3'-untranslated region (3'UTR) of mRNAs and prevent protein accumulation by either repressing translation or inducing mRNA degradation. Examples of specific mRNAs undergoing miRNA-mediated repression are numerous, but whether the repression is a reversible process remains largely unknown. Here, we show that cationic amino acid transporter 1 (CAT-1) mRNA and reporters bearing the CAT-1 3'UTR or its fragments can be relieved from the miRNA miR-122-induced inhibition in human hepatoma cells in response to different stress conditions. The derepression of CAT-1 mRNA is accompanied by its release from cytoplasmic processing bodies (P bodies) and its recruitment to polysomes, indicating that P bodies act as storage sites for mRNAs inhibited by miRNAs. The derepression requires binding of HuR, an AU-rich-element-binding ELAV family protein, to the 3'UTR of CAT-1 mRNA. We propose that proteins interacting with the 3'UTR will generally act as modifiers altering the potential of miRNAs to repress gene expression.

• Authors: S N Bhattacharyya, R Habermacher, U Martine, E I Closs, W Filipowicz
• Journal: Cold Spring Harbor symposia on quantitative biology (Cold Spring Harb Symp Quant Biol) Vol. 71 Pg. 513-21 ( 2006) ISSN: 0091-7451 [Print] United States
• PMID: 17381334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• 3' Untranslated Regions
• Amino Acids
• Cationic Amino Acid Transporter 1
• MicroRNAs
• RNA, Messenger
• RNA-Binding Proteins
• SLC7A1 protein, human

Topics

• 3' Untranslated Regions
• Amino Acids (metabolism)
• Cationic Amino Acid Transporter 1 (genetics, metabolism)
• Cell Line
• Cytoplasmic Structures (metabolism)
• Humans
• MicroRNAs (genetics, metabolism)
• Models, Biological
• Polyribosomes (metabolism)
• RNA, Messenger (genetics, metabolism)
• RNA-Binding Proteins (metabolism)
• Up-Regulation