Slippy-Sloppy translation: a tale of programmed and induced-ribosomal frameshifting

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.

Automated summary

Programmed ribosomal frameshifting (PRF) is a crucial mechanism used by viruses to replicate and regulate gene expression. Recent studies have found that ribosomes in many types of human cancer cells are prone to frameshifting under amino acid shortage, resulting in the production of aberrant proteins that may trigger T cell activation.