Ribosomes undergo an unanticipated movement (‘sliding’) while translating homopolymeric A sequences, which provides a biochemical rationale for the observation that iterated AAA codons are under-represented in gene-coding sequences.
Substitutions in general translation initiation factor eIF1A found as recurring somatic mutations in uveal melanoma destabilize the closed conformation of the preinitiation complex at the start codon and increase discrimination against suboptimal initiation codons genome-wide.
Despite billions of years of divergence, a majority of prokaryotic genes can functionally replace their essential eukaryotic counterparts, revealing broad preservation of ancestral functions and identifying heme biosynthesis as a near-universally swappable pathway.
Genomic-profiles and reporters reveal that the three-nucleotide ‘words’ read by the ribosome, codons, have a strong effect on mRNA stability, impacting the homeostatic mRNA and protein levels in human cells.
The small subunit ribosomal protein uS7/Rps5 interacts with translation initiation factor eIF2α to stabilize first the open, and then the closed conformation of the pre-initiation complex to promote accurate start codon selection in vivo.