XRN2 Autoregulation and Control of Polycistronic Gene Expresssion in Caenorhabditis elegans

PLoS Genet. 2016 Sep 15;12(9):e1006313. doi: 10.1371/journal.pgen.1006313. eCollection 2016 Sep.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / biosynthesis
  • Caenorhabditis elegans Proteins / genetics*
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics*
  • Exoribonucleases / antagonists & inhibitors
  • Exoribonucleases / genetics*
  • Gene Expression Regulation
  • Genes / genetics
  • Homeostasis / genetics
  • Nucleotidases / genetics*
  • Operon / genetics
  • Synthetic Lethal Mutations / genetics


  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • PAXT-1 protein, C elegans
  • Exoribonucleases
  • XRN-2 protein, C elegans
  • Nucleotidases
  • bisphosphoadenylate 3'-nucleotidase

Grants and funding

This work was supported by the Swiss National Science Foundation (SNF 31003A_143313), to HG (www.snf.ch) and the Novartis Research Foundation through Friedrich Miescher Institute for Biomedical Research Stiftung (www.fmi.ch). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.