Structural basis and function of XRN2 binding by XTB domains

Nat Struct Mol Biol. 2016 Feb;23(2):164-71. doi: 10.1038/nsmb.3155. Epub 2016 Jan 18.


The RNase XRN2 is essential in RNA metabolism. In Caenorhabditis elegans, XRN2 functions with PAXT-1, which shares a putative XRN2-binding domain (XTBD) with otherwise unrelated mammalian proteins. Here, we characterize the structure and function of an XTBD-XRN2 complex. Although XTBD stably interconnects two XRN2 domains through numerous interacting residues, mutation of a single critical residue suffices to disrupt XTBD-XRN2 complexes in vitro and to recapitulate paxt-1-null mutant phenotypes in vivo. Demonstrating conservation of function, vertebrate XTBD-containing proteins bind XRN2 in vitro, and human CDKN2AIPNL (HsC2AIL) can substitute for PAXT-1 in vivo. In vertebrates, which express three distinct XTBD-containing proteins, XRN2 may partition into distinct stable heterodimeric complexes, which probably differ in subcellular localization or function. In C. elegans, complex formation with PAXT-1, the sole XTBD protein, serves to preserve the stability of XRN2 in the absence of substrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / chemistry
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Crystallography, X-Ray
  • Exoribonucleases / chemistry
  • Exoribonucleases / metabolism*
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • Thermodynamics


  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • PAXT-1 protein, C elegans
  • Exoribonucleases
  • XRN-2 protein, C elegans