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  RNA helicase DDX1 converts RNA G-quadruplex structures into R-loops to promote IgH class switch recombination

de Almeida, C. R., Dhir, S., Dhir, A., Moghaddam, A. E., Sattentau, Q., Meinhart, A., et al. (2018). RNA helicase DDX1 converts RNA G-quadruplex structures into R-loops to promote IgH class switch recombination. Molecular Cell, 1-22. doi:10.1016/j.molcel.2018.04.001.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-4A7A-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-8968-0
Genre: Journal Article

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MolCell_70_2018_001.pdf (Any fulltext), 4MB
 
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 Creators:
de Almeida , Claudia Ribeiro, Author
Dhir, Somdutta, Author
Dhir, Ashish, Author
Moghaddam, Amin E., Author
Sattentau, Quentin, Author
Meinhart, Anton1, Author              
Proudfoot, Nicholas J., Author
Affiliations:
1Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society, ou_1497700              

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Free keywords: DEAD-box RNA helicase 1; G-quadruplexes; R-loops; activation-induced cytidine deaminase; class switch recombination
 Abstract: Class switch recombination (CSR) at the immunoglobulin heavy-chain (IgH) locus is associated with the formation of R-loop structures over switch (S) regions. While these often occur co-transcriptionally between nascent RNA and template DNA, we now show that they also form as part of a post-transcriptional mechanism targeting AID to IgH S-regions. This depends on the RNA helicase DDX1 that is also required for CSR in vivo. DDX1 binds to G-quadruplex (G4) structures present in intronic switch transcripts and converts them into S-region R-loops. This in turn targets the cytidine deaminase enzyme AID to S-regions so promoting CSR. Notably R-loop levels over S-regions are diminished by chemical stabilization of G4 RNA or by the expression of a DDX1 ATPase-deficient mutant that acts as a dominant-negative protein to reduce CSR efficiency. In effect, we provide evidence for how S-region transcripts interconvert between G4 and R-loop structures to promote CSR in the IgH locus.

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Language(s): eng - English
 Dates: 2018-03-022017-09-112018-03-302018-05-032018-05-03
 Publication Status: Published in print
 Pages: 22
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Molecular Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: 1 - 22 Identifier: ISSN: 1097-2765
CoNE: https://pure.mpg.de/cone/journals/resource/954925610929