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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
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