Briggs, E., Hamilton, G., Crouch, K. , Lapsley, C. and McCulloch, R. (2018) Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome. Nucleic Acids Research, 46(22), pp. 11789-11805. (doi: 10.1093/nar/gky928) (PMID:30304482) (PMCID:PMC6294496)
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Abstract
R-loops are stable RNA–DNA hybrids that have been implicated in transcription initiation and termination, as well as in telomere maintenance, chromatin formation, and genome replication and instability. RNA Polymerase (Pol) II transcription in the protozoan parasite Trypanosoma brucei is highly unusual: virtually all genes are co-transcribed from multigene transcription units, with mRNAs generated by linked trans-splicing and polyadenylation, and transcription initiation sites display no conserved promoter motifs. Here, we describe the genome-wide distribution of R-loops in wild type mammal-infective T. brucei and in mutants lacking RNase H1, revealing both conserved and diverged functions. Conserved localization was found at centromeres, rRNA genes and retrotransposon-associated genes. RNA Pol II transcription initiation sites also displayed R-loops, suggesting a broadly conserved role despite the lack of promoter conservation or transcription initiation regulation. However, the most abundant sites of R-loop enrichment were within the regions between coding sequences of the multigene transcription units, where the hybrids coincide with sites of polyadenylation and nucleosome-depletion. Thus, instead of functioning in transcription termination the most widespread localization of R-loops in T. brucei suggests a novel correlation with pre-mRNA processing. Finally, we find little evidence for correlation between R-loop localization and mapped sites of DNA replication initiation.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Crouch, Dr Kathryn and Briggs, Miss Emma and Hamilton, Dr Graham and Lapsley, Mr Craig and McCulloch, Professor Richard |
Authors: | Briggs, E., Hamilton, G., Crouch, K., Lapsley, C., and McCulloch, R. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Nucleic Acids Research |
Publisher: | Oxford University Press |
ISSN: | 0305-1048 |
ISSN (Online): | 1362-4962 |
Published Online: | 10 October 2018 |
Copyright Holders: | Copyright © 2018 The Authors |
First Published: | First published in Nucleic Acids Research 46(22): 11789-11805 |
Publisher Policy: | Reproduced under a Creative Commons License |
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