PAXT-1 promotes XRN2 activity by stabilizing it through a conserved domain

Mol Cell. 2014 Jan 23;53(2):351-60. doi: 10.1016/j.molcel.2014.01.001.


XRN2 is an essential eukaryotic exoribonuclease that processes and degrades various substrates. Here we identify the previously uncharacterized protein R05D11.6/PAXT-1 as a subunit of an XRN2 complex in C. elegans. Targeted paxt-1 inactivation through TALEN-mediated genome editing reduces XRN2 levels, decreases miRNA turnover activity, and results in worm death, which can be averted by overexpressing xrn-2. Hence, stabilization of XRN2 is a major function of PAXT-1. A truncated PAXT-1 protein retaining a predicted domain of unknown function (DUF3469) suffices to restore viability to paxt-1 mutant animals, elevates XRN2 levels, and binds to XRN2. This domain occurs in additional metazoan proteins and mediates interaction of human CDKN2AIP/CARF and NKRF/NRF with XRN2. Thus, we have identified a bona fide XRN2-binding domain (XTBD) that can link different proteins, and possibly functionalities, to XRN2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Binding Sites
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Conserved Sequence
  • DNA-Binding Proteins
  • Exoribonucleases / metabolism
  • Gene Knockout Techniques
  • Humans
  • Protein Structure, Tertiary
  • RNA Stability
  • RNA-Binding Proteins / metabolism
  • Repressor Proteins / metabolism
  • Transcription Factors / metabolism


  • Apoptosis Regulatory Proteins
  • CDKN2AIP protein, human
  • CaRF protein, human
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • NKRF protein, human
  • PAXT-1 protein, C elegans
  • RNA-Binding Proteins
  • Repressor Proteins
  • Transcription Factors
  • Exoribonucleases
  • XRN2 protein, human