RNA-binding protein AUF1 represses Dicer expression.
MicroRNA (miRNA) biogenesis is tightly regulated by numerous proteins. Among them, Dicer is required for the processing of the precursor (pre-)miRNAs into the mature miRNA. Despite its critical function, the mechanisms that regulate Dicer expression are not well understood. Here we report that the RNA-binding protein (RBP) AUF1 (AU-binding factor 1) associates with the endogenous DICER1 mRNA and can interact with several segments of DICER1 mRNA within the coding region (CR) and the 3'-untranslated region (UTR). Through these interactions, AUF1 lowered DICER1 mRNA stability, since silencing AUF1 lengthened DICER1 mRNA half-life and increased Dicer expression, while overexpressing AUF1 lowered DICER1 mRNA and Dicer protein levels. Given that Dicer is necessary for the synthesis of mature miRNAs, the lowering of Dicer levels by AUF1 diminished the levels of miRNAs tested, but not the levels of the corresponding pre-miRNAs. In summary, AUF1 suppresses miRNA production by reducing Dicer production.
Laboratory of Molecular Biology and Immunology, National Institute on Aging-Intramural Research Program, NIH, 251 Bayview Blvd., Baltimore, MD 21224, USA. abdelmohsenk@mail.nih.gov
Kotb
K
Abdelmohsen
Kumiko
K
Tominaga-Yamanaka
Subramanya
S
Srikantan
Je-Hyun
JH
Yoon
Min-Ju
MJ
Kang
Myriam
M
Gorospe
D020413:3' Untranslated Regions; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D035683:MicroRNAs; D012333:RNA, Messenger; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases