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Select Research Group Head Prof. Sir Tom Blundell Prof. Kevin Brindle Dr Bill Broadhurst Dr Guy Brown Dr Mark Carrington Prof. Paul Dupree Prof. Gerard Evan - Head of Dept Prof. Richard Farndale Dr Giorgio Favrin Dr Jenny Gallop Dr Nick Gay Dr Andrew Grace Dr Jules Griffin Dr Brian Hendrich Dr Andrew Hesketh Dr Robin Hesketh Dr Matt Higgins Dr Florian Hollfelder Dr Hee-Jeon Hong Prof. Chris Howe Dr Marko Hyvonen Prof. Steve Jackson Dr Tony Jackson Prof. Richard Jackson Prof. Ernest Laue Prof. Peter Leadlay Dr Kathryn Lilley Dr Karen Lipkow Dr Rick Livesey Prof. Ben Luisi Dr Sarah Lummis Dr Juan Mata Dr John McCafferty Prof. Jim Metcalfe Dr Masanori Mishima Dr Eric Miska Dr Tom Monie Dr Helen Mott Dr Natasha Murzina Dr Daniel Nietlispach Dr Darerca Owen Prof. Steve Oliver Dr Luca Pellegrini Dr Markus Ralser Dr Nick Robinson Prof. George Salmond Dr Deirdre Scadden Dr José Silva Prof. Austin Smith Prof. Chris Smith Dr Nancy Standart Prof. Dame Jean Thomas Dr Aviva Tolkovsky Dr Martin Welch Dr Joyce Wong Dr Nianshu Zhang

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Select by Subject or Manager DNA Sequencing Facility . . . . . Mr John Lester _______________________________ Quantitative Proteomics . . . . . Dr Kathryn Lilley _______________________________ Proteomics Core Services . . . . . Dr Mike Deery _______________________________ Protein & Nucleic Acid Chemistry . . . . . Dr Len Packman _______________________________ Metabolomics . . . . . Dr Jules Griffin _______________________________ Baculovirus Facility . . . . . Dr Darerca Owen _______________________________ Biophysics Facility . . . . . Dr Katherine Stott _______________________________ Crystallographic X-ray Facility . . . . . Dr Dima Chirgadze _______________________________ NMR spectroscopy . . . . . Dr Daniel Nietlispach _______________________________ Fermentation Facility . . . . . Dr Nianshu Zhang _______________________________ Bioinformatics & Computational Biology Services . . . . . Dr Jenny Barna _______________________________ Computer & IT Support . . . . . Dr Erik Timmers _______________________________

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Select past member of Department Dr Stephen Bell Prof. Jonathan Blackburn Dr David Brown Dr Pak-Lee Chau Dr Hal Dixon (deceased) Dr Jessica Downs Prof. David Ellar Dr Paul Kemp Dr Simon Lovell Dr Kenji Mizuguchi Dr Massimo Paoli Prof. Richard Perham Dr Peter Reynolds Dr Philip Rubery Dr Gerry Smith Dr Margaret Sunde Prof. Jamie Vandenberg Dr Kira Weissman

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Investigating the Fate of Hyper-Edited dsRNA

Research Groupings: Structural and molecular cell biology | Functional genomics, systems biology and genetic medicine

	ADARs catalyze A-to-I editing
	IU-dsRNA suppresses interferon induction and apoptosis

Our research is focused on understanding the roles that hyper-edited inosine-containing double stranded RNA plays in mammalian cells.

Adenosine deaminases acting on RNA (ADARs) catalyze the deamination of adenosine (A) to inosine (I) within double-stranded RNA (dsRNA).  Analysis of ADAR-null mutants has highlighted the importance of ADARs in post-transcriptional gene regulation.

While A-to-I editing can occur selectively within mRNA, hyper-editing of long dsRNA can result in up to 50% of A residues being changed to I.  As I is decoded as guanosine by ribosomes, A-to-I editing can result in codon changes.  Localized changes in RNA structure are also likely within hyper-edited inosine-containing dsRNAs (IU-dsRNAs), as IU pairs are weaker than conventional base pairs.  Most mammalian editing occurs within non-coding regions of RNA, including repetitive elements such as inverted Alus.  However, while countless RNAs may be extensively edited, the function of IU-dsRNA in cells is not fully understood.  Moreover, various studies have suggested diverse fates for IU-dsRNA.

We have shown that IU-dsRNA undergoes specific cleavage in various cell lysates, suggests that hyper-editing can tag dsRNA for subsequent destruction¹.  Furthermore, we have shown that the RISC subunit Tudor-SN specifically binds to IU-dsRNA and promotes its cleavage².  We have additionally shown that IU-dsRNA binds a stress-granule-like complex and downregulates both endogenous and reporter gene expression in trans³.  Recent analyses have demonstrated that IU-dsRNAs are sufficient to suppress interferon induction and apoptosis⁴.  Our current research aims to elucidate mechanisms underlying these observations.

Lab members
Siew-Kit Ng, Jenny Reed, Patrice Vitali, Rebekka Weißbach

References