Exon-dependent transcriptional adaptation by exon-junction complex proteins Y14/RNP-4 and MAGOH/MAG-1 in Caenorhabditis elegans

Transcriptional adaptation is a powerful gene regulation mechanism that can increase genetic robustness. Transcriptional adaptation occurs when a gene is mutated and is mediated by the mutant RNA, rather than by protein feedback loops. We show here that transcriptional adaptation occurs in the C. elegans clh family of Cl- channels and that it requires exon-junction complex (EJC) proteins RNP-4, MAG-1, and eiF4AIII. Depending on which exons are deleted in distinct clh-1 alleles, different clh genes are regulated in an EJC-dependent manner. Our results support the idea that different transcriptional adaptation outcomes may be directed by the differential interaction of the EJC with its target mutant RNAs. Author summary The expansion of molecular tools designed to introduce mutations in genes across different models has revealed that sometimes mutations do not cause any apparent phenotype. This phenomenon is called genetic robustness and it can be mediated by the mechanism of transcriptional adaptation. In transcriptional adaptation, the degradation of the mutant RNA causes the up or downregulation of genes that functionally compensate for the mutant gene. Using the genetically amenable nematode C. elegans, we show here that transcriptional adaptation depends on proteins of the Exon Junction Complex, a protein complex important for RNA stability and localization, and protein translation. Further, we show that different mutations of the same gene lead to different transcriptional adaptation outcomes and variable functional compensation. Our results bring new insights into the still poorly understood phenomenon of transcriptional adaptation.

Automated summary

Transcriptional adaptation is a gene regulation mechanism that increases genetic stability. This study reveals the occurrence of transcriptional adaptation in the C. elegans clh family of Cl- channels, which requires the involvement of exon-junction complex (EJC) proteins. Different clh genes are regulated by the EJC in different ways.