Regulation of non ‐canonical proteins from diverse origins through the nonsense‐mediated mRNA decay pathway

This study investigates the impact ofUPF1-knockdown on the expression of non-canonical/mutant proteins, employing proteogenomic to exploreUPF1 role within the NMD pathway. Additionally, we conducted a comprehensive pan-cancer analysis ofUPF1 expression and evaluatedUPF1 expression in Triple-Negative Breast Cancer (TNBC) tissuein-vivo. Our findings reveal thatUPF1-knockdown leads to increased translation of non-canonical/mutant proteins, particularly those originating from retained-introns, pseudogenes, long non-coding RNAs, and unannotated transcript biotypes. Moreover, our analysis demonstrates elevatedUPF1 expression in various cancer types, with notably heightened protein levels in patient-derived TNBC tumors compared to adjacent tissues. This study elucidatesUPF1 role in mitigating transcriptional noise by degrading transcripts encoding non-canonical/mutant proteins. Targeting this mechanism may reveal a new spectrum of neoantigens accessible to the antigen presentation pathway. Our novel findings provide a strong foundation for the development of therapeutic strategies aimed at targetingUPF1 or modulating the NMD pathway.
Source: Proteomics - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research