Translational repression by RNA-binding protein TIAR.
The RNA-binding protein TIAR has been proposed to inhibit protein synthesis transiently by promoting the formation of translationally silent stress granules. Here, we report the selective binding of TIAR to several mRNAs encoding translation factors such as eukaryotic initiation factor 4A (eIF4A) and eIF4E (translation initiation factors), eEF1B (a translation elongation factor), and c-Myc (which transcriptionally controls the expression of numerous translation regulatory proteins). TIAR bound the 3'-untranslated regions of these mRNAs and potently suppressed their translation, particularly in response to low levels of short-wavelength UV (UVC) irradiation. The UVC-imposed global inhibition of the cellular translation machinery was significantly relieved after silencing of TIAR expression. We propose that the TIAR-mediated inhibition of translation factor expression elicits a sustained repression of protein biosynthesis in cells responding to stress.
Laboratory of Cellular and Molecular Biology, Box 12, LCMB, National Institute on Aging-Intramural Research Program, National Institutes of Health, 5600 Nathan Shock Dr., Baltimore, Maryland 21224, USA.
Krystyna
K
Mazan-Mamczarz
Ashish
A
Lal
Jennifer L
JL
Martindale
Tomoko
T
Kawai
Myriam
M
Gorospe
D039642:Eukaryotic Initiation Factors / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D039642:Eukaryotic Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C076751:TIAL1 protein, human