CRD-BP Protects the Coding Region of βTrCP1 mRNA from miR-183-Mediated Degradation

Abstract

miRNAs are largely known to base-pair with the 3′UTR of target mRNAs, downregulating their stability and translation. mRNA of βTrCP1 ubiquitin ligase is very unstable, but unlike the majority of mRNAs where 3′UTR determines the rate of mRNA turnover, βTrCP1 mRNA contains cis-acting destabilizing elements within its coding region. Here we show that degradation of mRNA of βTrCP1 is miRNA-dependent, and identified miR-183 as a microRNA that interacts with the coding region of βTrCP1 mRNA. Argonaute2 interacts with the same region of βTrCP1 mRNA in miR-183-dependent manner. Inhibition of mir-183 function or disruption of mir-183-binding site stabilizes βTrCP1 mRNA and elevates βTrCP1 levels, resulting in activation of the SCFβTrCP E3 ubiquitin ligase. We have previously shown that RNA-binding protein, CRD-BP, binds to the coding region of βTrCP1 mRNA and stabilizes it. In this report we demonstrate that CRD-BP prevents degradation of βTrCP1 mRNA by attenuating its miR-183-dependent interaction with Ago2.

mir-35 is involved in intestine cell G1/S transition and germ cell proliferation in C. elegans

“…For instance, miR-17 and miR-20a temper an E2F1-induced G1 checkpoint [47], and miR-195 regulates G1/S transition [48]. Additionally, miR-18 mediates the degradation of βTrCP1 (mammalian lin-23 homolog) mRNA, which encodes the main component of the SCF complex [49]. Together with our findings in C. elegans intestine, it appears that posttranscriptional regulation of G1/S transition by miRNAs is well conserved across species.…”

MiRNA-27a controls FBW7/hCDC4-dependent cyclin E degradation and cell cycle progression

“…1,31 Indeed, it is becoming increasingly clear that miRNA function often depends on other factors such as RNAbinding proteins. [32][33][34] For example, the interaction between the cyclin-dependent kinase inhibitor p27 mRNA and the miRNAs miR-221/miR-222 is dynamically regulated by the RNA-binding protein Pumilio-1. 35 Future studies using the FBW7-3'UTR as a bait for the identification of RNA-binding proteins as well as ©2 0 1 1 L a n d e s B i o s c i e n c e .…”

Mechanism of translational regulation by miR-2 from sites in the 5′ untranslated region or the open reading frame

“…This striking positional bias has led to the development of miR target search algorithms that focus on 39UTRs and, consequently, to a further amplification of the bias for functional 39UTR sites (Bartel 2009). However, effective miR-binding sites have also been identified in the 59UTR or the open reading frame (ORF) of target mRNAs (e.g., Jopling et al 2005;Duursma et al 2008;Forman et al 2008;Henke et al 2008;Lal et al 2008;Ørom et al 2008;Tay et al 2008;Elcheva et al 2009;Tsai et al 2009). Non-39UTR miR targeting has also been studied in silico and in reporter gene assays (e.g., Kloostermann et al 2004;Lytle et al 2007;Stark et al 2007).…”