CRD-BP protects the coding region of betaTrCP1 mRNA from miR-183-mediated degradation.
miRNAs are largely known to base pair with the 3'UTR of target mRNAs, downregulating their stability and translation. mRNA of betaTrCP1 ubiquitin ligase is very unstable, but unlike the majority of mRNAs where 3'UTR determines the rate of mRNA turnover, betaTrCP1 mRNA contains cis-acting destabilizing elements within its coding region. Here we show that degradation of mRNA of betaTrCP1 is miRNA dependent and identify miR-183 as a microRNA that interacts with the coding region of betaTrCP1 mRNA. Argonaute2 interacts with the same region of betaTrCP1 mRNA in an miR-183-dependent manner. Inhibition of miR-183 function or disruption of the miR-183-binding site stabilizes betaTrCP1 mRNA and elevates betaTrCP1 levels, resulting in activation of the SCF(betaTrCP) E3 ubiquitin ligase. We previously showed that the RNA-binding protein CRD-BP binds to the coding region of betaTrCP1 mRNA and stabilizes it. Here we demonstrate that CRD-BP prevents degradation of betaTrCP1 mRNA by attenuating its miR-183-dependent interaction with Ago2.
Elcheva
Irina
I
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
Goswami
Srikanta
S
Noubissi
Felicite K
FK
Spiegelman
Vladimir S
VS
D060565:Argonaute Proteins; D001665:Binding Sites; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000502:physiology*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics / Q000378:metabolism*
C466422:AGO2 protein, human; D060565:Argonaute Proteins; C471644:BTRC protein, human; D015852:Eukaryotic Initiation Factor-2; C406144:IGF2BP1 protein, human; C533449:MIRN183 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D011993:Recombinant Fusion Proteins; D044844:beta-Transducin Repeat-Containing Proteins; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases