title: XRN2 Autoregulation and Control of Polycistronic Gene Expresssion in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Takashi S
authors.identifier: 0000-0003-3715-7039
authors.initials: TS
authors.lastname: Miki
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|Swiss Institute of Bioinformatics, Basel, Switzerland.
authors.forename: Sarah H
authors.identifier: 0000-0003-3927-2559
authors.initials: SH
authors.lastname: Carl
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.|Swiss Institute of Bioinformatics, Basel, Switzerland.
authors.forename: Michael B
authors.identifier: 0000-0002-2269-4934
authors.initials: MB
authors.lastname: Stadler
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Helge
authors.identifier: 0000-0002-8169-6905
authors.initials: H
authors.lastname: Großhans
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D005095:Exoribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics*; D005786:Gene Expression Regulation; D005796:Genes / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D009708:Nucleotidases / Q000235:genetics*; D009876:Operon / Q000235:genetics; D000072020:Synthetic Lethal Mutations / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C000608560:PAXT-1 protein, C elegans; D005095:Exoribonucleases; C544213:XRN-2 protein, C elegans; D009708:Nucleotidases; C053354:bisphosphoadenylate 3'-nucleotidase