A Specialized Mechanism of Translation Mediated by FXR1a-Associated MicroRNP in Cellular Quiescence

作者：Bukhari Syed I A; Truesdell Samuel S; Lee Sooncheol; Kollu Swapna; Classon Anthony; Boukhali Myriam; Jain Esha; Mortensen Richard D; Yanagiya Akiko; Sadreyev Ruslan I; Haas Wilhelm; Vasudevan Shobha^*

来源：Molecular Cell, 2016, 61(5): 760-773.

DOI：10.1016/j.molcel.2016.02.013

MicroRNAs predominantly decrease gene expression; however, specific mRNAs are translationally upregulated in quiescent (G0) mammalian cells and immature Xenopus laevis oocytes by an FXR1a-associated microRNA-protein complex (microRNP) that lacks the microRNP repressor, GW182. Their mechanism in these conditions of decreased mTOR signaling, and therefore reduced canonical (cap-and-poly(A)-tail-mediated) translation, remains undiscovered. Our data reveal that mTOR inhibition in human THP1 cells enables microRNA-mediated activation. Activation requires shortened/no poly(A)tail targets; polyadenylated mRNAs are partially activated upon PAIP2 overexpression, which interferes with poly(A)-bound PABP, precluding PABP-enhanced microRNA-mediated inhibition and canonical translation. Consistently, inhibition of PARN deadenylase prevents activation. P97/DAP5, a homolog of canonical translation factor, eIF4G, which lacks PABP-and cap binding complex-interacting domains, is required for activation, and thereby for the oocyte immature state. P97 interacts with 30 UTR-binding FXR1a-associated microRNPs and with PARN, which binds mRNA 50 caps, forming a specialized complex to translate recruited mRNAs in these altered canonical translation conditions.

• 出版日期2016-3-3
• 单位McGill