Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs.pdf

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2017-04-06 发布于江苏
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Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs.pdf

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Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs

Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs Ashish Lal, Krystyna Mazan-Mamczarz, Tomoko Kawai, Xiaoling Yang, Jennifer L Martindale and Myriam Gorospe* Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, MD, USA RNA-binding proteins HuR and AUF1 bind to many com- mon AU-rich target mRNAs and exert opposing influence on target mRNA stability, but the functional interactions between HuR and AUF1 have not been systematically studied. Here, using common target RNAs encoding p21 and cyclin D1, we provide evidence that HuR and AUF1 can bind target transcripts on both distinct, nonoverlap- ping sites, and on common sites in a competitive fashion. In the nucleus, both proteins were found together within stable ribonucleoprotein complexes; in the cytoplasm, HuR and AUF1 were found to bind to target mRNAs individually, HuR colocalizing with the translational ap- paratus and AUF1 with the exosome. Our results indicate that the composition and fate (stability, translation) of HuR- and/or AUF1-containing ribonucleoprotein com- plexes depend on the target mRNA of interest, RNA-bind- ing protein abundance, stress condition, and subcellular compartment. The EMBO Journal (2004) 23, 3092–3102. doi:10.1038/ sj.emboj.7600305; Published online 15 July 2004 Subject Categories: RNA Keywords: exosome; mRNA stability; polysome; RNA- binding protein; RNA motif Introduction Post-transcriptional processes such as RNA splicing, and mRNA export, stability, and translation are emerging as critical mechanisms of gene regulation in mammalian cells. These regulatory programs are primarily governed by RNA- binding proteins (RBPs) that associate with pre-mRNAs and mRNAs and ensure their proper processing (splicing, 50 end and 30 end modifications, export) as well as their subcyto- plasmic transit, half-life, and translation rate. Specialized RBPs that bind specific mRNA subsets have received inc