부산대학교 도서관

Programmed ribosomal frameshifting (PRF) is a key mechanism that viruses use to generate essential proteins for replication, and as a means of regulating gene expression. PRF generally involves recoding signals or frameshift stimulators to elevate the occurrence of frameshifting at shift-prone 'slippery' sequences. Given its essential role in viral replication, targeting PRF was envisioned as an attractive tool to block viral infection. However, in contrast to controlled-PRF mechanisms, recent studies have shown that ribosomes of many human cancer cell types are prone to frameshifting upon amino acid shortage; thus, these cells are deemed to be sloppy. The resulting products of a sloppy frameshift at the 'hungry' codons are aberrant proteins the degradation and display of which at the cell surface can trigger T cell activation. In this review, we address recent discoveries in ribosomal frameshifting and their functional consequences for the proteome in human cancer cells. Programmed ribosomal frameshifting (PRF) is a common mechanism in viruses whereby translating ribosomes shift coding reading frames at specific mRNA locations, producing multiple proteins essential for virus maturation. Targeting PRF in viruses can be used to control virus replication, as recently suggested for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). As opposed to PRF, ribosomal frameshifting can also be triggered by amino acid availability in yeast and human cancers. Cancer-induced deregulation of the mitogen-activated protein kinase (MAPK)/mammalian target of rapamycin (mTOR) pathway promotes ribosomal frameshifting upon acute shortage of tryptophan. The aberrant proteins produced by deregulated translation at the tryptophan codons can be presented at the cell surface to provoke a specific T cell recognition. [ABSTRACT FROM AUTHOR]