XRN2 Autoregulation and Control of Polycistronic Gene Expresssion in Caenorhabditis elegans

Xrn2 is a conserved 5’→3’ exoribonuclease that complexes with proteins that contain xrn2-binding domains (xtbds). in caenorhabditis elegans (c. elegans),the xtbd-protein paxt-1 stabilizes xrn2 to retain its activity. xrn2 activity is also promoted by 3'(2'),5'-bisphosphate nucleotidase 1 (bpnt1) through hydrolysis of an endogenous xrn inhibitor 3’-phosphoadenosine-5'-phosphate (pap). here,we find through unbiased screening that loss of bpnt-1 function suppresses lethality caused by paxt-1 deletion. this unexpected finding is explained by xrn2 autoregulation,which occurs through repression of a cryptic promoter activity and destabilization of the xrn-2 transcript. de-repression appears to be triggered such that more robust xrn2 perturbation,by elimination of both paxt-1 and bpnt1,is less detrimental to worm viability than absence of paxt-1 alone. indeed,we find that two distinct xrn2 repression mechanisms are alleviated at different thresholds of xrn2 inactivation. like more than 15% of c. elegans genes,xrn-2 occurs in an operon,and we identify additional operons under its control,consistent with a broader function of xrn2 in polycistronic gene regulation. regulation occurs through intercistronic regions that link genes in an operon,but a part of the mechanisms may allow xrn2 to operate on monocistronic genes in organisms lacking operons. © 2016 miki et al.