Alternate RNA decoding results in stable and abundant proteins in mammals

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 26, 2024

Amino acid substitutions may substantially alter protein stability and function, but the contribution of arising from alternate translation (deviations genetic code) is unknown. To explore it, we analyzed deep proteomic transcriptomic data over 1,000 human samples, including 6 cancer types 26 healthy tissues. This global analysis identified 60,024 high confidence corresponding to 8,801 unique sites in proteins derived 1,990 genes. Some are shared across while others exhibit strong tissue-type specificity. Surprisingly, products more abundant than their canonical counterparts for hundreds proteins, suggesting sense codon recoding. Recoded include transcription factors, proteases, signaling associated with neurodegeneration. Mechanisms contributing substitution abundance stability, frequency, codon-anticodon mismatches, RNA modifications. We characterize sequence motifs around alternatively translated amino acids how ratios vary domains, tissue cancers. The positively intrinsically disordered regions polymorphisms gnomAD, though cannot account substitutions. Both tissue-specificity conserved between mouse. These results demonstrate diversifying mammalian proteomes, its association tissue-specific diseases.

Язык: Английский

Nanopore signal deviations from pseudouridine modifications in RNA are sequence-specific: quantification requires dedicated synthetic controls

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Сен. 28, 2024

Язык: Английский