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Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM.

<div class='caption-title'>RUVBL1-RUVBL2 interacts with DHX34.</div>
<div class='caption-title'>Testing the interaction between RUVBL1-RUVBL2 and NMD factors.</div>
<div class='caption-title'>Cryo-EM of the RUVBL1-RUVBL2-DHX34 complex.</div>
López-Perrote A, Hug N, González-Corpas A, Rodríguez CF, Serna M, García-Martín C, Boskovic J, Fernandez-Leiro R, Caceres JF, Llorca O
OpenAccess logo Elife 9 (2020)
Cited: 7 times
EuropePMC logo PMID: 33205750

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 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.

Articles - 7aho mentioned but not cited (1)

  1. Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM. López-Perrote A, Hug N, González-Corpas A, Rodríguez CF, Serna M, García-Martín C, Boskovic J, Fernandez-Leiro R, Caceres JF, Llorca O. Elife 9 e63042 (2020)


Reviews citing this publication (1)

  1. Translation-coupled mRNA quality control mechanisms. Monaghan L, Longman D, Cáceres JF. EMBO J 42 e114378 (2023)

Articles citing this publication (5)

  1. A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation. Hug N, Aitken S, Longman D, Raab M, Armes H, Mann AR, Rio-Machin A, Fitzgibbon J, Rouault-Pierre K, Cáceres JF. RNA 28 1224-1238 (2022)
  2. CryoEM of RUVBL1-RUVBL2-ZNHIT2, a complex that interacts with pre-mRNA-processing-splicing factor 8. Serna M, González-Corpas A, Cabezudo S, López-Perrote A, Degliesposti G, Zarzuela E, Skehel JM, Muñoz J, Llorca O. Nucleic Acids Res 50 1128-1146 (2022)
  3. Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder. Marques AR, Santos JX, Martiniano H, Vilela J, Rasga C, Romão L, Vicente AM. Biomedicines 10 665 (2022)
  4. Hippocalcin-Like 1 blunts liver lipid metabolism to suppress tumorigenesis via directly targeting RUVBL1-mTOR signaling. Chen T, Yuan Z, Lei Z, Duan J, Xue J, Lu T, Yan G, Zhang L, Liu Y, Li Q, Zhang Y. Theranostics 12 7450-7464 (2022)
  5. Proteomic Landscape of Human Sperm in Patients with Different Spermatogenic Impairments. Becker LS, Al Smadi MA, Raeschle M, Rishik S, Abdul-Khaliq H, Meese E, Abu-Halima M. Cells 12 1017 (2023)


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