Stress-induced reversal of microRNA repression and mRNA P-body localization in human cells.
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.
Bhattacharyya
S N
SN
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Habermacher
R
R
Martine
U
U
Closs
E I
EI
Filipowicz
W
W
D020413:3' Untranslated Regions; D000596:Amino Acids / Q000378:metabolism; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D022083:Cytoplasmic Structures / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D011132:Polyribosomes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D015854:Up-Regulation
D020413:3' Untranslated Regions; D000596:Amino Acids; D027201:Cationic Amino Acid Transporter 1; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C420825:SLC7A1 protein, human