TY - JOUR
T1 - Mechanism of the AAA+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs
AU - Machado-Pinilla, Rosario
AU - Liger, Dominique
AU - Leulliot, Nicolas
AU - Meier, U. Thomas
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - AAA+ ATPase
KW - Dyskeratosis congenita
KW - NAP57/dyskerin
KW - Telomerase
KW - snoRNP
UR - http://www.scopus.com/inward/record.url?scp=84866604898&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866604898&partnerID=8YFLogxK
U2 - 10.1261/rna.034942.112
DO - 10.1261/rna.034942.112
M3 - Article
C2 - 22923768
AN - SCOPUS:84866604898
SN - 1355-8382
VL - 18
SP - 1833
EP - 1845
JO - RNA
JF - RNA
IS - 10
ER -