LINKING mRNA TRANSLATION TO CELL CYCLE PROGRESSION: A LESSON FROM WARS-1

Abstract

The dysregulation of mRNA translation is common in tumors, attributed to the heightened protein synthesis demands and rapid proliferation of cancer cells. Genetic mutations in key genes associated with protein translation are frequently observed in cancer patients. Despite ongoing efforts, the exact connection between mRNA translation defects and cancer progression remains uncertain. A crucial aspect of protein translation involves binding of the amino acids to their cognate tRNA, a process facilitated by a set of proteins known as Aminoacyl tRNA synthetases (AARS). In cancer patients, both gain-of-function and loss-of-function mutation in the tryptophanyl tRNA synthetase 1 (WARS1), a member of the AARS family, is frequently detected and strongly linked to metastasis. Studies involving the knockdown of wars-1 in C. elegans have demonstrated disruptions in germ cell mitosis and cell cycle arrest at the G2/M phase transition, regulated by the cyclin-dependent kinase 1 (CDK-1). Furthermore, our lab has revealed that the depletion of WARS-1 results in massive genomic catastrophe, as indicated by chromosomal abnormalities, chromatin bridges, and micronuclei formation. Using RNA sequencing, we have identified crucial key players in the aforementioned process, including proteins involved in protein translation, DNA damage repair, and cell cycle progression to be significantly downregulated upon WARS-1 depletion.

Date of Award	2024
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences