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Citation
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HERO ID
387379
Reference Type
Journal Article
Title
The Nematode eIF4E/G Complex works with a Trans-spliced Leader Stem Loop to Enable Efficient Translation of Trimethylguanosine-capped RNAs
Author(s)
Wallace, A; Filbin, ME; Veo, B; McFarland, C; Stepinski, J; Jankowska-Anyszka, M; Darzynkiewicz, E; Davis, RE
Year
2010
Is Peer Reviewed?
1
Journal
Molecular and Cellular Biology
ISSN:
0270-7306
EISSN:
1098-5549
Language
English
DOI
10.1128/mcb.01437-09
Abstract
Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5' end through the eIF4F initiation complex binding to the 5' m(7)G-mRNA cap. Spliced leader RNA trans-splicing adds a trimethylguanosine (TMG) cap and sequence, the spliced leader (SL), to the 5' end of mRNAs. Efficient translation of TMG-capped mRNAs in nematodes requires the spliced leader sequence. Here we define a core set of nucleotides and stem loop within the 22 nt nematode SL that stimulates translation of mRNAs with a TMG cap. The structure and core nucleotides are conserved in other nematode spliced leaders and correspond to regions of SL1 required for early C. elegans development. These SL elements do not facilitate translation of m(7)G-capped RNAs in nematodes or TMG-capped mRNAs in mammalian or plant translation systems. Similar stem loop structures are predicted in phylogenetically diverse SLs. We show that the nematode eIF4E/G complex enables efficient translation of the TMG-SL RNAs in diverse in vitro translation systems. TMG-capped mRNA translation is determined by eIF4E/G interaction with the cap and the SL RNA, although the SL does not increase eIF4E/G's affinity for capped RNA. These studies suggest the mRNA 5' UTR can play a positive and novel role in translation initiation through interaction with the eIF4E/G complex in nematodes, and raises the question of whether eIF4E/G-RNA interactions may play a role in the translation of other eukaryotic mRNAs.
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