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

Julien Champagne, Kelly Mordente, Remco Nagel, Reuven Agami*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)1123-1133
Number of pages11
JournalTrends in Genetics
Issue number11
Publication statusPublished - Nov 2022

Bibliographical note

R.A. is supported by the Dutch Cancer Society (KWF projects 13647, 11574) and the European Research Council (ERC-AdG #832844). We would like to express our thanks to all of the members of the Agami laboratory for very fruitful discussions.

Publisher Copyright: © 2022 Elsevier Ltd


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