Requirement of CSR-1 isoforms and catalytic activity for C. elegans lifespan.

The C. elegans CSR-1 encodes an essential Argonaute protein that binds to 22 nucleotide small guide RNA to regulate germline gene expression. Recent characterization of the two CSR-1 isoforms (a and b) have demonstrated tissue-specific expression and functions. Here, we found that loss of function to the csr-1 a isoform has minimal effect on lifespan while a mutant with deletion to both csr-1 a and csr-1 b isoforms shows a significant decrease in lifespan. Furthermore, we found that single copy expression of a slicing inactive variant of csr-1 fails to rescue the shortened lifespan. Overall, the data here provide new information on the requirement of isoform and domain-specific contribution of CSR-1 to C. elegans lifespan.