An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31789591.
- Also identified by DOI 10.7554/eLife.48246 and PMC identifier 6887119.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Loading of mRNA onto the ribosomal 43S pre-initiation complex (PIC) and its subsequent scanning require the removal of the secondary structure of the by RNA helicases such as eIF4A. However, the topology and mechanics of the scanning complex bound to mRNA (48S-PIC) and the influence of its solvent-side composition on the scanning process are poorly known. Here, we found that the ES6S region of the 48S-PIC constitutes an extended binding channel for eIF4A-mediated unwinding of mRNA and scanning. Blocking ES6S inhibited the cap-dependent translation of mRNAs that have structured 5' UTRs (including G-quadruplexes), many of which are involved in signal transduction and growth, but it did not affect IRES-driven translation. Genome-wide analysis of mRNA translation revealed a great diversity in ES6S-mediated scanning dependency. Our data suggest that mRNA threading into the ES6S region makes scanning by 48S PIC slower but more processive. Hence, we propose a topological and functional model of the scanning 48S-PIC.
Medical subject headings
- Eukaryotic Initiation Factor-4F
- RNA Helicases
- RNA, Messenger
- Saccharomyces cerevisiae Proteins
- Transduction, Genetic