Structure of the 80S ribosome-Xrn1 nuclease complex

Nat Struct Mol Biol. 2019 Apr;26(4):275-280. doi: 10.1038/s41594-019-0202-5. Epub 2019 Mar 25.


Messenger RNA (mRNA) homeostasis represents an essential part of gene expression, in which the generation of mRNA by RNA polymerase is counter-balanced by its degradation by nucleases. The conserved 5'-to-3' exoribonuclease Xrn1 has a crucial role in eukaryotic mRNA homeostasis by degrading decapped or cleaved mRNAs post-translationally and, more surprisingly, also co-translationally. Here we report that active Xrn1 can directly and specifically interact with the translation machinery. A cryo-electron microscopy structure of a programmed Saccharomyces cerevisiae 80S ribosome-Xrn1 nuclease complex reveals how the conserved core of Xrn1 enables binding at the mRNA exit site of the ribosome. This interface provides a conduit for channelling of the mRNA from the ribosomal decoding site directly into the active center of the nuclease, thus separating mRNA decoding from degradation by only 17 ± 1 nucleotides. These findings explain how rapid 5'-to-3' mRNA degradation is coupled efficiently to its final round of mRNA translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism*
  • Exoribonucleases / ultrastructure
  • RNA, Messenger / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Ribosomes / ultrastructure
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / ultrastructure


  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Exoribonucleases
  • XRN1 protein, S cerevisiae