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TitleRegulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateNov 18, 2020
AuthorsAndres López-Perrote / Nele Hug / Ana González-Corpas / Carlos F Rodríguez / Marina Serna / Carmen García-Martín / Jasminka Boskovic / Rafael Fernandez-Leiro / Javier F Caceres / Oscar Llorca /
PubMed AbstractNonsense-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 ...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.
External linksElife / PubMed:33205750 / PubMed Central
MethodsEM (single particle)
Resolution4.18 - 4.97 Å
Structure data

EMDB-11788:
Cryo-EM structure of the RUVBL1-RUVBL2-DHX34 complex
Method: EM (single particle) / Resolution: 4.97 Å

11789

7aho

EMDB-11789, PDB-7aho:
RUVBL1-RUVBL2 heterohexameric ring after binding of RNA helicase DHX34
Method: EM (single particle) / Resolution: 4.18 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Source
  • homo sapiens (human)
KeywordsTRANSLATION / RUVBL1-RUVBL2 / DHX34 / Nonsense-Mediated mRNA Decay / RNA degradation / Cryo-EM

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