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-Structure paper
Title | Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM. |
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Journal, issue, pages | Elife, Vol. 9, Year 2020 |
Publish date | Nov 18, 2020 |
Authors | Andres 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 Abstract | 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 ...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 links | Elife / PubMed:33205750 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.18 - 4.97 Å |
Structure data | EMDB-11788: EMDB-11789, PDB-7aho: |
Chemicals | ChemComp-ADP: |
Source |
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Keywords | TRANSLATION / RUVBL1-RUVBL2 / DHX34 / Nonsense-Mediated mRNA Decay / RNA degradation / Cryo-EM |