Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome.
Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome.
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DOI：
10.1093/nar/gky928
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发表时间：
2018-12-14
影响因子：
14.9
通讯作者：
McCulloch R
中科院分区：
文献类型：
--
作者：
Briggs E;Hamilton G;Crouch K;Lapsley C;McCulloch R
R 环是稳定的 RNA-DNA 杂合体，与转录起始和终止、端粒维持、染色质形成以及基因组复制和不稳定性有关。原生动物寄生虫布氏锥虫中的 RNA 聚合酶 (Pol) II 转录非常不寻常：几乎所有基因都是由多基因转录单元共同转录的，通过连接的反式剪接和多聚腺苷酸化生成 mRNA，并且转录起始位点不显示保守的启动子基序。在这里，我们描述了野生型哺乳动物感染性布氏锥虫和缺乏 RNase H1 的突变体中 R 环的全基因组分布，揭示了保守和不同的功能。在着丝粒、rRNA 基因和逆转录转座子相关基因处发现了保守定位。 RNA Pol II 转录起始位点也显示出 R 环，表明尽管缺乏启动子保守性或转录起始调控，但其作用广泛保守。然而，最丰富的R环富集位点位于多基因转录单元的编码序列之间的区域内，其中杂合体与多聚腺苷酸化和核小体耗尽的位点一致。因此，T. brucei 中 R 环最广泛的定位并不是在转录终止中起作用，这表明与前 mRNA 加工存在新的相关性。最后，我们几乎没有发现 R 环定位与 DNA 复制起始映射位点之间相关性的证据。
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.
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影响因子：
3.8
作者：
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DOI：
10.1016/j.tig.2016.10.002
发表时间：
2016-12
期刊：
Trends in genetics : TIG
影响因子：
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作者：
Chédin F
通讯作者：
Chédin F