Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs.
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.
Lal
Ashish
A
Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, MD 21224, USA.
Mazan-Mamczarz
Krystyna
K
Kawai
Tomoko
T
Yang
Xiaoling
X
Martindale
Jennifer L
JL
Gorospe
Myriam
M
D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005786:Gene Expression Regulation / Q000528:radiation effects; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020871:RNA Stability; D012333:RNA, Messenger / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014158:Transcription, Genetic / Q000528:radiation effects; D014466:Ultraviolet Rays
D000954:Antigens, Surface; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D019938:Cyclin D1