Evasion of nonsense-mediated mRNA decay by the Rous sarcoma virus RNA stability element

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NHLBI	MOLBIO-4

Authors

• Z. Ge
• J.R. Hogg

Abstract

Nonsense-mediated mRNA decay (NMD) is an mRNA quality control pathway in eukaryotes that degrades mRNAs containing premature termination codons. Global analyses of targets of NMD, together with experiments using model mRNAs, suggest that 3’UTR length is an important determinant of transcript susceptibility to NMD. The NMD factor Upf1 mediates decay target selection by associating with NMD-sensitive 3’UTRs in an RNA length-dependent manner. Preferential accumulation of Upf1 on mRNAs containing long 3’UTRs is predicted to increase the probability of Upf1 interacting with release factors during translation termination, potentiating the mRNA for NMD. We are investigating a retroviral RNA element capable of protecting mRNAs containing long 3’UTRs from Upf1-dependent decay. The RNA stability element (RSE) of Rous sarcoma virus is a large (~ 400 nt) RNA segment that resides immediately downstream of the viral gag termination codon, preventing it from being recognized as premature. Using biochemical and functional assays, we are exploring the mechanistic basis for the RSE’s protective activity. Our results show that the RSE is able to protect synthetic reporter mRNAs containing long 3’UTRs from NMD in mammalian cells. Furthermore, our data suggest that the RSE’s inhibitory effect on NMD originates from its ability to prevent Upf1 binding to 3’UTRs.

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