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; Myriam Gorospe

doi:10.1038/sj.emboj.7600305

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

EMBO J. 2004 Aug 4;23(15):3092-102. doi: 10.1038/sj.emboj.7600305. Epub 2004 Jul 15.

Authors

Ashish Lal¹, Krystyna Mazan-Mamczarz, Tomoko Kawai, Xiaoling Yang, Jennifer L Martindale, Myriam Gorospe

Affiliation

¹ Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, MD 21224, USA.

Abstract

RNA-binding proteins HuR and AUF1 bind to many common 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, nonoverlapping 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 apparatus and AUF1 with the exosome. Our results indicate that the composition and fate (stability, translation) of HuR- and/or AUF1-containing ribonucleoprotein complexes depend on the target mRNA of interest, RNA-binding protein abundance, stress condition, and subcellular compartment.

MeSH terms

Antigens, Surface / genetics
Antigens, Surface / metabolism*
Cell Cycle Proteins / genetics
Cyclin D1 / genetics
Cyclin-Dependent Kinase Inhibitor p21
ELAV Proteins
ELAV-Like Protein 1
Gene Expression Regulation / radiation effects
HeLa Cells
Heterogeneous Nuclear Ribonucleoprotein D0
Heterogeneous-Nuclear Ribonucleoprotein D / genetics
Heterogeneous-Nuclear Ribonucleoprotein D / metabolism*
Humans
RNA Stability*
RNA, Messenger / chemical synthesis
RNA, Messenger / genetics
RNA, Messenger / metabolism*
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism*
Substrate Specificity
Transcription, Genetic / radiation effects
Ultraviolet Rays

Substances

Antigens, Surface
CDKN1A protein, human
Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor p21
ELAV Proteins
ELAV-Like Protein 1
ELAVL1 protein, human
HNRNPD protein, human
Heterogeneous Nuclear Ribonucleoprotein D0
Heterogeneous-Nuclear Ribonucleoprotein D
RNA, Messenger
RNA, Small Interfering
RNA-Binding Proteins
Cyclin D1