Briggs, E., Crouch, K. , Lemgruber, L. , Lapsley, C. and McCulloch, R. (2018) Ribonuclease H1-targeted R-loops in surface antigen gene expression sites can direct trypanosome immune evasion. PLoS Genetics, 14(12), e1007729. (doi: 10.1371/journal.pgen.1007729) (PMID:30543624) (PMCID:PMC6292569)
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Abstract
Switching of the Variant Surface Glycoprotein (VSG) in Trypanosoma brucei provides a crucial host immune evasion strategy that is catalysed both by transcription and recombination reactions, each operating within specialised telomeric VSG expression sites (ES). VSG switching is likely triggered by events focused on the single actively transcribed ES, from a repertoire of around 15, but the nature of such events is unclear. Here we show that RNA-DNA hybrids, called R-loops, form preferentially within sequences termed the 70 bp repeats in the actively transcribed ES, but spread throughout the active and inactive ES, in the absence of RNase H1, which degrades R-loops. Loss of RNase H1 also leads to increased levels of VSG coat switching and replication-associated genome damage, some of which accumulates within the active ES. This work indicates VSG ES architecture elicits R-loop formation, and that these RNA-DNA hybrids connect T. brucei immune evasion by transcription and recombination.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Crouch, Dr Kathryn and Briggs, Miss Emma and Lemgruber Soares, Dr Leandro and Lapsley, Mr Craig and McCulloch, Professor Richard |
Creator Roles: | Briggs, E.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – original draft, Writing – review and editing Crouch, K.Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing – original draft, Writing – review and editing Lemgruber, L.Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – review and editing Lapsley, C.Investigation, Methodology, Validation McCulloch, R.Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review and editing |
Authors: | Briggs, E., Crouch, K., Lemgruber, L., Lapsley, C., and McCulloch, R. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | PLoS Genetics |
Publisher: | Public Library of Science |
ISSN: | 1553-7390 |
ISSN (Online): | 1553-7404 |
Copyright Holders: | Copyright © 2018 Briggs et al. |
First Published: | First published in PLoS Genetics 14(12): e1007729 |
Publisher Policy: | Reproduced under a Creative Commons License |
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