figshare
Browse

File(s) not publicly available

The C-terminal domain of eukaryotic protein synthesis initiation factor (eIF4G is sufficient to support cap-independent translation in the absence ofeIF4E

journal contribution
posted on 2023-06-07, 20:05 authored by T Ohlmann, M Rau, V M Pain, Simon Morley
The foot and mouth disease virus, a picornavirus, encodes two forms of a cysteine proteinase (leader or L protease) that bisects the eIF4G polypeptide of the initiation factor complex eIF4F into N-terminal (N(t)) and C-terminal (C(t)) domains. Previously we showed that, although in vitro cleavage of the translation initiation factor, eIF4G, with L protease decreases cap-dependent translation, the cleavage products themselves may directly promote cap-independent protein synthesis. We now demonstrate that translation of uncapped mRNAs normally exhibits a strong requirement for eIF4E. However, this dependence is abolished when eIF4G is cleaved, with the C(t) domain capable of supporting translation in the absence of the N(t) domain. In contrast, the efficient translation of the second cistron of bicistronic mRNAs, directed by two distinct Internal Ribosome Entry Segments (IRES), exhibits no requirement for eIF4E but is dependent upon either intact eIF4G or the C(t) domain. These results demonstrate that: (i) the apparent requirement for eIF4F for internal initiation on IRES-driven mRNAs can be fulfilled by the C(t) proteolytic cleavage product; (ii) when eIF4G is cleaved, the C(t) domain can also support cap-independent translation of cellular mRNAs not possessing an IRES element, in the absence of eIF4E; and (iii) when eIF4G is intact, translation of cellular mRNAs, whether capped or uncapped, is strictly dependent upon eIF4E. These data complement recent work in other laboratories defining the binding sites for other initiation factors on the eIF4G molecule.

History

Publication status

  • Published

Journal

EMBO Journal

ISSN

0261-4189

Publisher

Nature Publishing Group

Issue

6

Volume

15

Page range

1371-1382

ISBN

0261-4189

Department affiliated with

  • Biochemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC