Mechanism of the AAA+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs

Rosario Machado-Pinilla, Dominique Liger, Nicolas Leulliot, U. Thomas Meier

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The AAA+ ATPases pontin and reptin function in a staggering array of cellular processes including chromatin remodeling, transcriptional regulation, DNA damage repair, and assembly of macromolecular complexes, such as RNA polymerase II and small nucleolar (sno) RNPs. However, the molecular mechanism for all of these AAA+ ATPase associated activities is unknown. Here we document that, during the biogenesis of H/ACA RNPs (including telomerase), the assembly factor SHQ1 holds the pseudouridine synthase NAP57/dyskerin in a viselike grip, and that pontin and reptin (as components of the R2TP complex) are required to pry NAP57 from SHQ1. Significantly, the NAP57 domain captured by SHQ1 harbors most mutations underlying X-linked dyskeratosis congenita (X-DC) implicating the interface between the two proteins as a target of this bone marrow failure syndrome. Homing in on the essential first steps of H/ACA RNP biogenesis, our findings provide the first insight into the mechanism of action of pontin and reptin in the assembly of macromolecular complexes.

Original languageEnglish (US)
Pages (from-to)1833-1845
Number of pages13
JournalRNA
Volume18
Issue number10
DOIs
StatePublished - Oct 2012

Fingerprint

Macromolecular Substances
Adenosine Triphosphatases
Dyskeratosis Congenita
Chromatin Assembly and Disassembly
RNA Polymerase II
Telomerase
Hand Strength
DNA Repair
DNA Damage
Mutation
NAP57
Proteins
pseudouridine synthases
Bone Marrow failure syndromes

Keywords

  • AAA+ ATPase
  • Dyskeratosis congenita
  • NAP57/dyskerin
  • snoRNP
  • Telomerase

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Mechanism of the AAA+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs. / Machado-Pinilla, Rosario; Liger, Dominique; Leulliot, Nicolas; Meier, U. Thomas.

In: RNA, Vol. 18, No. 10, 10.2012, p. 1833-1845.

Research output: Contribution to journalArticle

Machado-Pinilla, Rosario ; Liger, Dominique ; Leulliot, Nicolas ; Meier, U. Thomas. / Mechanism of the AAA+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs. In: RNA. 2012 ; Vol. 18, No. 10. pp. 1833-1845.
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