Bi-directional ribosome scanning controls the stringency of start codon selection.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34782646.
- Also identified by DOI 10.1038/s41467-021-26923-3 and PMC identifier 8593136.
- 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
The fidelity of start codon recognition by ribosomes is paramount during protein synthesis. The current knowledge of eukaryotic translation initiation implies unidirectional 5'→3' migration of the pre-initiation complex (PIC) along the 5' UTR. In probing translation initiation from ultra-short 5' UTR, we report that an AUG triplet near the 5' end can be selected via PIC backsliding. Bi-directional ribosome scanning is supported by competitive selection of closely spaced AUG codons and recognition of two initiation sites flanking an internal ribosome entry site. Transcriptome-wide PIC profiling reveals footprints with an oscillation pattern near the 5' end and start codons. Depleting the RNA helicase eIF4A leads to reduced PIC oscillations and impaired selection of 5' end start codons. Enhancing the ATPase activity of eIF4A promotes nonlinear PIC scanning and stimulates upstream translation initiation. The helicase-mediated PIC conformational switch may provide an operational mechanism that unifies ribosome recruitment, scanning, and start codon selection.
Medical subject headings
- Codon, Initiator
- Peptide Chain Initiation, Translational
- Protein Biosynthesis
- Ribosomes