azyx-1 is a new gene that overlaps with zyxin and affects its translation in C. elegans, impacting muscular integrity and locomotion

Overlapping genes are widely prevalent; however, their expression and consequences are poorly understood. Here, we describe and functionally characterize a novel zyx-1 overlapping gene, azyx-1 , with distinct regulatory functions in Caenorhabditis elegans . We observed conservation of alternative open reading frames (ORFs) overlapping the 5′ region of zyxin family members in several animal species, and find shared sites of azyx-1 and zyxin proteoform expression in C . elegans . In line with a standard ribosome scanning model, our results support cis regulation of zyx-1 long isoform(s) by upstream initiating azyx-1a . Moreover, we report on a rare observation of trans regulation of zyx-1 by azyx-1 , with evidence of increased ZYX-1 upon azyx-1 overexpression. Our results suggest a dual role for azyx-1 in influencing zyx-1 proteoform heterogeneity and highlight its impact on C . elegans muscular integrity and locomotion.