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Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Mol+Cell 2016 ; 61 (5): 760-73 Nephropedia Template TP
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A specialized mechanism of translation mediated by FXR1a-associated microRNP in cellular quiescence #MMPMID26942679
Bukhari SI; Truesdell SS; Lee S; Kollu S; Classon A; Boukhali M; Jain E; Mortensen RD; Yanagiya A; Sadreyev RI; Haas W; Vasudevan S
Mol Cell 2016[Mar]; 61 (5): 760-73 PMID26942679show ga
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 microRNP (microRNA-protein complex) 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 3?-UTR-binding FXR1a-associated microRNPs and with PARN, which binds mRNA 5? caps, forming a specialized complex to translate recruited mRNAs in these altered canonical translation conditions.