40S ribosomal subunits scan mRNA for the start codon by one-dimensional diffusion.

During eukaryotic translation initiation, the small (40S) ribosomal subunit is recruited to the 5' cap and subsequently scans the 5' untranslated region (5' UTR) of mRNA in search of the start codon. The molecular mechanism of mRNA scanning remains unclear. Here, using GFP reporters in cells, we show that order-of-magnitude variations in the lengths of unstructured 5' UTRs have a modest effect on protein synthesis.

Sitravatinib combined with PD-1 blockade enhances cytotoxic T-cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a leading cause of cancer-related mortality. Sitravatinib is a novel multi-gene tyrosine kinase inhibitor (TKI) that targets tumor-associated macrophage (TAM) receptors, VEGF, PDGF and c-Kit. Currently, sitravatinib is actively being studied in clinical trials across solid tumors and other TKIs have shown efficacy in combination with immune checkpoint inhibitors (ICI) in cancer models.

Frameshifting at collided ribosomes is modulated by elongation factor eEF3 and by integrated stress response regulators Gcn1 and Gcn20.

Ribosome stalls can result in ribosome collisions that elicit quality control responses, one function of which is to prevent ribosome frameshifting, an activity that entails the interaction of the conserved yeast protein Mbf1 with uS3 on colliding ribosomes. However, the full spectrum of factors that mediate frameshifting during ribosome collisions is unknown. To delineate such factors in the yeast , we used genetic selections for mutants that affect frameshifting from a known ribosome stall site, CGA codon repeats.

Conservation of location of several specific inhibitory codon pairs in the Saccharomyces sensu stricto yeasts reveals translational selection.

Synonymous codons provide redundancy in the genetic code that influences translation rates in many organisms, in which overall codon use is driven by selection for optimal codons. It is unresolved if or to what extent translational selection drives use of suboptimal codons or codon pairs. In Saccharomyces cerevisiae, 17 specific inhibitory codon pairs, each comprised of adjacent suboptimal codons, inhibit translation efficiency in a manner distinct from their constituent codons, and many are translated slowly in native genes.

Multi-protein bridging factor 1(Mbf1), Rps3 and Asc1 prevent stalled ribosomes from frameshifting.

Reading frame maintenance is critical for accurate translation. We show that the conserved eukaryotic/archaeal protein Mbf1 acts with ribosomal proteins Rps3/uS3 and eukaryotic Asc1/RACK1 to prevent frameshifting at inhibitory CGA-CGA codon pairs in the yeast . Mutations in that allow frameshifting implicate eukaryotic conserved residues near the mRNA entry site.