Translation of TNFAIP2 is tightly controlled by upstream open reading frames

Cellular and Molecular Life Sciences : CMLS
Anica ScholzTobias Schmid

Abstract

Translation is a highly regulated process, both at the global as well as on a transcript-specific level. Regulatory upstream open reading frames (uORFs) represent a mode to alter cap-dependent translation efficiency in a transcript-specific manner and are found in numerous mRNAs. In the majority of cases, uORFs inhibit the translation of their associated main ORFs. Consequently, their inactivation results in enhanced translation of the main ORF, a phenomenon best characterized in the context of the integrated stress response. In the present study, we identified potent translation-inhibitory uORFs in the transcript leader sequence (TLS) of tumor necrosis factor alpha induced protein 2 (TNFAIP2). The initial description of the uORFs was based on the observation that despite a massive induction of TNFAIP2 mRNA expression in response to interleukin 1β (IL1β), TNFAIP2 protein levels remained low in MCF7 cells. While we were able to characterize the uORFs with respect to their exact size and sequential requirements in this cellular context, only TPA stimulation partially overcame the translation-inhibitory activity of the TNFAIP2 uORFs. Characterization of TNFAIP2 translation in the context of monocyte-to-macrophage differentiation s...Continue Reading

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Citations

May 28, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G Melissa KrishnathasIris Bischoff-Kont

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Methods Mentioned

BETA
PCR
transfection
ribo-seq

Software Mentioned

STAR
bowtie2
cutadapt
Tools
uORF

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