Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 298 (5592), 419-22

Separable Roles for rent1/hUpf1 in Altered Splicing and Decay of Nonsense Transcripts

Affiliations

Separable Roles for rent1/hUpf1 in Altered Splicing and Decay of Nonsense Transcripts

Joshua T Mendell et al. Science.

Abstract

The mechanism by which disruption of reading frame can influence pre-messenger RNA (pre-mRNA) processing is poorly understood. We assessed the role of factors essential for nonsense-mediated mRNA decay (NMD) in nonsense-mediated altered splicing (NAS) with the use of RNA interference (RNAi) in mammalian cells. Inhibition of rent1/hUpf1 expression abrogated both NMD and NAS of nonsense T cell receptor beta transcripts. In contrast, inhibition of rent2/hUpf2 expression did not disrupt NAS despite achieving comparable stabilization of nonsense transcripts. We also demonstrate that NAS and NMD are genetically separable functions of rent1/hUpf1. Additionally, rent1/hUpf1 enters the nucleus where it may directly influence early events in mRNA biogenesis. This provides compelling evidence that NAS relies on a component of the nonsense surveillance machinery but is not an indirect consequence of NMD.

Comment in

Similar articles

See all similar articles

Cited by 122 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback