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

Julien Champagne, Kelly Mordente, Remco Nagel, Reuven Agami

Journal: Trends in genetics : TIG 2022;38(11):1123-1133

PMID: 35641342

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.; Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands; Erasmus MC, Rotterdam University, Rotterdam, The Netherlands. Electronic address: [email protected].

DOI: 10.1016/j.tig.2022.05.009

Link outs

Subscription / membership required

Full Text Sources:

MeSH Terms: Amino Acids, Codon, Frameshifting, Ribosomal, Humans, Proteome, Ribosomes