Like every other cell in the human body, cancer cells also produce their own share of proteins for survival. During this production process, cells often encounter a glitch called ribosomal frameshifting. This exceptionally rare event occurs roughly once in every 100,000 translation events, when the ribosome, while reading genetic instructions to make a protein, shifts its reading position. A recent Nature study investigated whether this protein-building glitch in cancer cells can be turned into a targeted cancer therapy.

Ribosomes read mRNA in groups of three genetic letters, known as codons. To find out where this reading process goes wrong, the researchers developed high-throughput dual-luciferase reporter libraries containing randomized genetic sequences. This allowed them to systematically track instances where ribosomes slipped out of their usual reading frame.

The ribosome profiler pinpointed specific codon pairs, such as AGAACG, that frequently trigger ribosomes to slip backward by one letter (a −1 frameshift) in cancer cells. Noncancerous cells, however, read these sequences normally.