A novel overlapping geneazyx-1affects the translation of zyxin inC. elegans

Overlapping genes are widely prevalent, however, their expression and consequences are poorly understood. Here, we describe and functionally characterize a novelzyx-1overlapping gene,azyx-1, with distinct regulatory functions inC. elegans. We observed conservation of alternative open reading frames overlapping the 5’ region of zyxin family members in several animal species, and find shared sites ofazyx-1and zyxin proteoform expression inC. elegans. In line with a standard ribosome scanning model, our results supportcisregulation ofzyx-1long isoform(s) by upstream initiatingazyx-1a. Moreover, we report on a rare observation oftransregulation ofzyx-1byazyx-1, with evidence of increased ZYX-1 uponazyx-1overexpression. Our results suggest a dual role forazyx-1in influencingzyx-1proteoform heterogeneity and highlights its impact onC. elegansmuscular integrity and locomotion.