2026-07-23T22:58:37Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/124982024-11-29T23:46:41Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

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 López-Perrote, Andres author Hug, Nele author González-Corpas, Ana author Rodríguez, Carlos F author García-Martín, Carmen author Caceres, Javier F author Llorca, Oscar author Fernandez-Leiro, Rafael 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. 10.7554/eLife.63042 2050-084X eLife 33205750 http://hdl.handle.net/20.500.12105/12498 Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM.