2026-05-22T16:45:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65032024-11-29T23:06:26Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Toribio, René
author
Díaz-López, Irene
author
Boskovic, Jasminka
author
Ventoso, Ivan
funder
Ministerio de Ciencia e Innovación (España)
2018-10-23T12:17:53Z
2018-10-23T12:17:53Z
2018-05-04
Nucleic Acids Res. 2018; 46 (8): 4176-4187.
10.1093/nar/gky071
1362-4962
0305-1048
Nucleic acids research
29415133
http://hdl.handle.net/20.500.12105/6503
The topology and dynamics of the scanning ribosomal 43S pre-initiation complex (PIC) bound to mRNA and initiation factors (eIFs) are probably the least understood aspects of translation initiation in eukaryotes. Recently, we described a trapping mechanism in alphavirus that stalls the PIC during scanning of viral mRNA. Using this model, we were able to snapshot for the first time the eIF4A helicase bound to mRNA in a 48S initiation complex assembled in vitro. This interaction was only detected in the presence of the natural stem loop structure (DLP) located downstream from the AUG in viral mRNA that promoted stalling of the PIC, suggesting that DLP stability was enough to jam the helicase activity of eIF4A in a fraction of assembled 48S complexes. However, a substantial proportion of DLP mRNA molecules were effectively unwound by eIF4A in vitro, an activity that alphaviruses counteract in infected cells by excluding eIF4A from viral factories. Our data indicated that eIF4A-mRNA contact occurred in (or near) the ES6S region of the 40S subunit, suggesting that incoming mRNA sequences penetrate through the ES6S region during the scanning process. We propose a topological model of the scanning PIC and how some viruses have exploited this topology to translate their mRNAs with fewer eIF requirements.
eng
43S PREINITIATION COMPLEX
SECONDARY STRUCTURE
HELICASE ACTIVITY
CODON SELECTION
FACTOR 4A
FACTOR 4G
EIF4A
MECHANISM
RIBOSOME
INHIBITION
Translation initiation of alphavirus mRNA reveals new insights into the topology of the 48S initiation complex
journal article
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translationinitiationofalphavirus_2018.pdf
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translationinitiationofalphavirus_2018.pdf.txt