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Review
. 2018 Feb;45(1):39-55.
doi: 10.1007/s11033-017-4139-7. Epub 2017 Dec 27.

Upf proteins: highly conserved factors involved in nonsense mRNA mediated decay

Puneet Gupta  1   2 , Yan-Ruide Li  3   4
Affiliations
Review

Upf proteins: highly conserved factors involved in nonsense mRNA mediated decay

Puneet Gupta et al. Mol Biol Rep. 2018 Feb.

Abstract

Over 10% of genetic diseases are caused by mutations that introduce a premature termination codon in protein-coding mRNA. Nonsense-mediated mRNA decay (NMD) is an essential cellular pathway that degrades these mRNAs to prevent the accumulation of harmful partial protein products. NMD machinery is also increasingly appreciated to play a role in other essential cellular functions, including telomere homeostasis and the regulation of normal mRNA turnover, and is misregulated in numerous cancers. Hence, understanding and designing therapeutics targeting NMD is an important goal in biomedical science. The central regulator of NMD, the Upf1 protein, interacts with translation termination factors and contextual factors to initiate NMD specifically on mRNAs containing PTCs. The molecular details of how these contextual factors affect Upf1 function remain poorly understood. Here, we review plausible models for the NMD pathway and the evidence for the variety of roles NMD machinery may play in different cellular processes.

Keywords: Nonsense-mediated mRNA decay; RNA quality control; Upf1 protein; Upf2 protein; Upf3 protein; mRNA degradation; mRNA surveillance.

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