2024-03-29T15:04:05Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/124982024-01-24T22:00:04Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
López-Perrote, Andres
author
Hug, Nele
author
González-Corpas, Ana
author
Rodríguez, Carlos F
author
Serna, Marina
author
García-Martín, Carmen
author
Caceres, Javier F
author
Llorca, Oscar
author
Boskovic, Jasminka
author
Fernandez-Leiro, Rafael
author
Llorca Blanco, Oscar Antonio
author
2020-11-18
Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs and also regulates the expression of a wide range of physiological transcripts. RUVBL1 and RUVBL2 AAA-ATPases form an hetero-hexameric ring that is part of several macromolecular complexes such as INO80, SWR1, and R2TP. Interestingly, RUVBL1-RUVBL2 ATPase activity is required for NMD activation by an unknown mechanism. Here, we show that DHX34, an RNA helicase regulating NMD initiation, directly interacts with RUVBL1-RUVBL2 in vitro and in cells. Cryo-EM reveals that DHX34 induces extensive changes in the N-termini of every RUVBL2 subunit in the complex, stabilizing a conformation that does not bind nucleotide and thereby down-regulates ATP hydrolysis of the complex. Using ATPase-deficient mutants, we find that DHX34 acts exclusively on the RUVBL2 subunits. We propose a model, where DHX34 acts to couple RUVBL1-RUVBL2 ATPase activity to the assembly of factors required to initiate the NMD response.
Elife. 2020 ;9:e63042.
http://hdl.handle.net/20.500.12105/12498
33205750
10.7554/eLife.63042
2050-084X
eLife
Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM.