Coordinated Ribosomal ITS2 RNA Processing by the Las1 Complex Integrating Endonuclease, Polynucleotide Kinase, and Exonuclease Activities

Mol Cell. 2015 Dec 3;60(5):808-815. doi: 10.1016/j.molcel.2015.10.021.


The rapidly evolving internal transcribed spacer 2 (ITS2) in the pre-ribosomal RNA is one of the most commonly applied phylogenetic markers at species and genus level. Yet, during ribosome biogenesis ITS2 is removed in all eukaryotes by a common, but still unknown, mechanism. Here we describe the existence of an RNA processome, assembled from four conserved subunits, Las1-Grc3-Rat1-Rai1, that carries all the necessary RNA processing enzymes to mediate coordinated ITS2 rRNA removal. Las1 is the long-sought-after endonuclease cleaving 27SB pre-rRNA at site C2 to yield a 5'-OH end at the 26S pre-rRNA and 2',3' cyclic phosphate at the 3' end of 7S pre-rRNA. Subsequently, polynucleotide kinase Grc3 catalyzes ATP-dependent 5'-OH phosphorylation of 26S pre-rRNA, which in turn enables Rat1-Rai1 exonuclease to generate 25S' pre-rRNA. ITS2 processing is reminiscent of tRNA splicing, but instead of subsequent tRNA ligation, the Las1 complex carries along an exonuclease tool to degrade the ITS2 rRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Ribosomal Spacer / metabolism*
  • Exoribonucleases / metabolism
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / metabolism
  • RNA, Fungal / metabolism
  • RNA, Ribosomal / metabolism
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*


  • DNA, Ribosomal Spacer
  • LAS1 protein, S cerevisiae
  • Multiprotein Complexes
  • Nuclear Proteins
  • RNA, Fungal
  • RNA, Ribosomal
  • RNA-Binding Proteins
  • Rai1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • RAT1 protein, S cerevisiae
  • Exoribonucleases