Translational Repression by RNA-Binding Protein TIAR

Abstract

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.

Supplemental material for this article may be found at http://mcb.asm.org/.

We thank K. G. Becker and the NIA Array Facility for providing cDNA arrays for analysis and S. Galbán and R. van Huizen for valuable discussions.

This research was supported by the Intramural Research Program of the NIA, NIH.