Single-molecule tracking reveals dynamic regulation of ribosomal scanning.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39356761.
- Also identified by DOI 10.1126/sciadv.adm9801 and PMC identifier 11446271.
- Licence recorded as CC BY-NC.
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Abstract
How eukaryotic ribosomes traverse messenger RNA (mRNA) leader sequences to search for protein-synthesis start sites remains one of the most mysterious aspects of translation and its regulation. While the search process is conventionally described by a linear "scanning" model, its exquisitely dynamic nature has restricted detailed mechanistic study. Here, we observed single <i>Saccharomyces cerevisiae</i> ribosomal scanning complexes in real time, finding that they scan diverse mRNA leaders at a rate of 10 to 20 nt s<sup>-1</sup>. We show that specific binding of a protein to its mRNA leader sequence substantially arrests scanning. Conversely, impairing scanning-complex guanosine 5'-triphosphate hydrolysis results in native start-site bypass. Our results illustrate an mRNA-centric, kinetically controlled regulatory model where the ribosomal pre-initiation complex amplifies a nuanced energetic landscape to regulate scanning and start-site selection fidelity.
Medical subject headings
- Ribosomes
- Saccharomyces cerevisiae
- RNA, Messenger