R2TP/Prefoldin-like Component RUVBL1/RUVBL2 Directly Interacts With ZNHIT2 to Regulate Assembly of U5 Small Nuclear Ribonucleoprotein

Nat Commun. 2017 May 31;8:15615. doi: 10.1038/ncomms15615.

Abstract

The R2TP/Prefoldin-like (R2TP/PFDL) complex has emerged as a cochaperone complex involved in the assembly of a number of critical protein complexes including snoRNPs, nuclear RNA polymerases and PIKK-containing complexes. Here we report on the use of multiple target affinity purification coupled to mass spectrometry to identify two additional complexes that interact with R2TP/PFDL: the TSC1-TSC2 complex and the U5 small nuclear ribonucleoprotein (snRNP). The interaction between R2TP/PFDL and the U5 snRNP is mostly mediated by the previously uncharacterized factor ZNHIT2. A more general function for the zinc-finger HIT domain in binding RUVBL2 is exposed. Disruption of ZNHIT2 and RUVBL2 expression impacts the protein composition of the U5 snRNP suggesting a function for these proteins in promoting the assembly of the ribonucleoprotein. A possible implication of R2TP/PFDL as a major effector of stress-, energy- and nutrient-sensing pathways that regulate anabolic processes through the regulation of its chaperoning activity is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism*
  • Alternative Splicing / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Energy Metabolism / genetics
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • RNA, Small Interfering / genetics
  • Ribonucleoprotein, U5 Small Nuclear / biosynthesis*
  • TOR Serine-Threonine Kinases / metabolism
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Carrier Proteins
  • Phosphoproteins
  • RNA, Small Interfering
  • Ribonucleoprotein, U5 Small Nuclear
  • TSC1 protein, human
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • ZNHIT2 protein, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL1 protein, human
  • RUVBL2 protein, human