Nonsense mediated decay induced by tethered human UPF3B is restricted to the cytoplasm.

Published

Journal Article

The subcellular localization of the nonsense mediated decay (NMD) of mRNA transcripts bearing premature termination codons has been controversial. Recently, it has been demonstrated that RNA tethering of key mediators of NMD, including human UPF3B, accurately recreates NMD. Here, we have used tethered UPF3B, combined with regulation of nuclear mRNA export using the retroviral Rev/RRE system, to examine where UPF3B-mediated mRNA degradation occurs. Our data clearly demonstrate that nuclear mRNA export is required for UPF3B-mediated degradation and moreover show that this degradation is exclusively cytoplasmic, despite the fact that the UPF3B fusion protein used is a nucleocytoplasmic shuttle protein localized predominantly to the nucleus. Moreover, exclusively cytoplasmic NMD occurred whether the target mRNA was exported via the retroviral Rev/RRE pathway or via the Tap: Nxt pathway used by most cellular mRNAs. These data may suggest that truly nuclear NMD, if it occurs, is at least in part mechanistically distinct from cytoplasmic NMD.

Full Text

Duke Authors

Cited Authors

  • Lu, S; Cullen, BR

Published Date

  • May 2004

Published In

Volume / Issue

  • 1 / 1

Start / End Page

  • 42 - 47

PubMed ID

  • 17194930

Pubmed Central ID

  • 17194930

Electronic International Standard Serial Number (EISSN)

  • 1555-8584

Language

  • eng

Conference Location

  • United States