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Nonsense-mediated mRNA decay occurs during eIF4F-dependent translation in human cells.

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.

journal_name

Nat Struct Mol Biol

journal_title

Nature structural & molecular biology

authors

Durand S,Lykke-Andersen J

doi

10.1038/nsmb.2575

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

702-9

issue

6

eissn

1545-9993

issn

1545-9985

pii

nsmb.2575

journal_volume

20

pub_type

杂志文章

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