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  A conserved structural element in the RNA helicase UPF1 regulates its catalytic activity in an isoform-specific manner

Gowravaram, M., Bonneau, F., Kanaan, J., Maciej, V. D., Fiorini, F., Raj, S., et al. (2018). A conserved structural element in the RNA helicase UPF1 regulates its catalytic activity in an isoform-specific manner. Nucleic Acids Research (London), 46(5), 2648-2659. doi:10.1093/nar/gky040.

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© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.

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 Creators:
Gowravaram, Manjeera1, Author
Bonneau, Fabien2, Author              
Kanaan, Joanne1, Author
Maciej, Vincent D.1, Author
Fiorini, Francesca1, Author
Raj, Saurabh1, Author
Croquette, Vincent1, Author
Le Hir, Herve1, Author
Chakrabarti, Sutapa1, Author
Affiliations:
1external, ou_persistent22              
2Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565144              

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Free keywords: EXON JUNCTION COMPLEX; MESSENGER-RNA; QUALITY-CONTROL; ATPASE ACTIVITY; PROTEIN; DECAY; MECHANISMS; FAMILY; EXPORT; COREBiochemistry & Molecular Biology;
 Abstract: The RNA helicase UPF1 is a key component of the nonsense mediated mRNA decay (NMD) pathway. Previous X-ray crystal structures of UPF1 elucidated the molecular mechanisms of its catalytic activity and regulation. In this study, we examine features of the UPF1 core and identify a structural element that adopts different conformations in the various nucleotide- and RNA-bound states of UPF1. We demonstrate, using biochemical and singlemolecule assays, that this structural element modulates UPF1 catalytic activity and thereby refer to it as the regulatory loop. Interestingly, there are two alternatively spliced isoforms of UPF1 in mammals which differ only in the lengths of their regulatory loops. The loop in isoform 1 (UPF11) is 11 residues longer than that of isoform 2. We find that this small insertion in UPF11 leads to a two-fold increase in its translocation and ATPase activities. To determine the mechanistic basis of this differential catalytic activity, we have determined the X-ray crystal structure of the helicase core of UPF11 in its apo-state. Our results point toward a novel mechanism of regulation of RNA helicases, wherein alternative splicing leads to subtle structural rearrangements within the protein that are critical to modulate enzyme movements and catalytic activity.

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Language(s): eng - English
 Dates: 2018-012018-03
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000427677100045
DOI: 10.1093/nar/gky040
 Degree: -

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Title: Nucleic Acids Research (London)
  Other : Nucleic Acids Res
Source Genre: Journal
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Publ. Info: Oxford : Oxford University Press
Pages: - Volume / Issue: 46 (5) Sequence Number: - Start / End Page: 2648 - 2659 Identifier: ISSN: 0305-1048
CoNE: https://pure.mpg.de/cone/journals/resource/110992357379342