Nonsense-mediated MRNA Decay Occurs During EIF4F-dependent Translation in Human Cells

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2013 May 14

PMID 23665580

Citations 56

Authors

Sebastien Durand

Jens Lykke-Andersen

Affiliations

Soon will be listed here.

Abstract

The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs undergoing premature termination of translation. It has been argued that in human cells, NMD is restricted to a pioneer round of translation initiated on mRNAs associated with the cap-binding complex (CBC) and that the exchange of the CBC for the eIF4F translation initiation complex renders mRNAs immune to NMD. Here, we demonstrate that human mRNAs undergoing eIF4F-dependent translation are not immune to NMD. First, prolonged translation inhibition does not render an NMD substrate resistant to NMD, despite allowing exchange of CBC for eIF4F. Second, eIF4F inhibitors stabilize NMD substrates undergoing cap-dependent translation. Third, the eIF4E-associated pool of an NMD substrate degrades as rapidly as the overall pool of the mRNA. Thus, eIF4F-dependent translation supports NMD in human cells, allowing for the possibility that NMD could be activated upon cellular cues on already translating mRNAs.

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