AI Article Synopsis
- * RUVBL1 and RUVBL2 are proteins that work together in a ring shape and are part of other important protein complexes.
- * The research shows that another protein, DHX34, interacts with RUVBL1-RUVBL2, changing their structure and helping to kickstart the NMD process by controlling their activity.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707835 | PMC |
| http://dx.doi.org/10.7554/eLife.63042 | DOI Listing |
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