Selective tRNA charging in breast cancer

Abstract

Increased tRNA abundance and amino acid coupling generally promote increased oncogenesis. By contrast, a new study shows that in breast cancer, the leucyl-tRNA synthetase LARS suppresses transformation and tumour development by increasing tRNA-Leu^CAG translation of certain tumour suppressor mRNAs.

Fig. 1 |. Downregulation of aminoacyl-tRNA synthetase LARS in breast cancer promotes transformation.

a, Leucine aminoacyl tRNA synthetase LARS covalently couples leucine (red dot) to cognate tRNAs, known as charging. Charged tRNAs are transported to elongating ribosomes by elongation factor eEF1A. b, Abundant charged tRNA-Leu^CAG results in unrestricted ribosome elongation on tumour suppressor EMP3, GGT5 and other mRNAs, reducing cell proliferation and inhibiting transformation. c, Reduced levels of LARS decreases the abundance of charged tRNA-Leu^CAG and translation of EMP3 and GGT5 tumour suppressor mRNAs, promoting increased cell proliferation and transformation. Two potential mechanisms are shown to account for reduced levels of EMP3 and GGT5 proteins upon limitation of tRNA-Leu^CAG levels. Increased ribosome dwell times at CUG and GUC leucine codons might specifically reduce translation of encoding mRNAs, or increase ribosome collisions, provoking cell signalling responses or protein folding responses that downregulate encoded protein synthesis.