Mitotic checkpoint gene expression is tuned by coding sequences

Abstract

AbstractThe mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Proper functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about SAC gene expression. Here, we show in fission yeast (S. pombe) that a combination of short mRNA half-lives and long protein half-lives supports stable SAC protein levels. For the SAC genes mad2+ and mad3+, their short mRNA half-lives depend on a high frequency of non-optimal codons and mRNA destabilization mediated through the RNA helicase Ste13 (S.c. Dhh1). In contrast, mad1+ mRNA half-life is short despite a relatively high frequency of optimal codons and despite the lack of known destabilizing motifs in its mRNA. Hence, although they are functionally related, different SAC genes employ different strategies of expression. Taken together, we propose that the codon usage of SAC genes is fine-tuned for proper SAC function. Our work shines light on the gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.