HuR recruits let-7/RISC to repress c-Myc expression.
RNA-binding proteins (RBPs) and microRNAs (miRNAs) are potent post-transcriptional regulators of gene expression. Here, we show that the RBP HuR reduced c-Myc expression by associating with the c-Myc 3' untranslated region (UTR) next to a miRNA let-7-binding site. Lowering HuR or let-7 levels relieved the translational repression of c-Myc. Unexpectedly, HuR and let-7 repressed c-Myc through an interdependent mechanism, as let-7 required HuR to reduce c-Myc expression and HuR required let-7 to inhibit c-Myc expression. Our findings suggest a regulatory paradigm wherein HuR inhibits c-Myc expression by recruiting let-7-loaded RISC (RNA miRNA-induced silencing complex) to the c-Myc 3'UTR.
Kim
Hyeon Ho
HH
Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. kimhye@grc.nia.nih.gov
Kuwano
Yuki
Y
Srikantan
Subramanya
S
Lee
Eun Kyung
EK
Martindale
Jennifer L
JL
Gorospe
Myriam
M
D020413:3' Untranslated Regions; D000954:Antigens, Surface / Q000378:metabolism*; D060565:Argonaute Proteins; D001483:Base Sequence; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism*
D020413:3' Untranslated Regions; C466422:AGO2 protein, human; D000954:Antigens, Surface; D060565:Argonaute Proteins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D015852:Eukaryotic Initiation Factor-2; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; C487931:mirnlet7 microRNA, human