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在布鲁氏锥虫中,细胞系特异性 RNA 编辑模式表明了一种在遗传突变不耐受的系统中产生蛋白质变异的独特机制。

Cell-line specific RNA editing patterns in Trypanosoma brucei suggest a unique mechanism to generate protein variation in a system intolerant to genetic mutations.

机构信息

Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.

出版信息

Nucleic Acids Res. 2020 Feb 20;48(3):1479-1493. doi: 10.1093/nar/gkz1131.

DOI:10.1093/nar/gkz1131
PMID:31840176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7026638/
Abstract

Trypanosoma brucei possesses a highly complex RNA editing system that uses guide RNAs to direct the insertion and deletion of uridines in mitochondrial mRNAs. These changes extensively alter the target mRNAs and can more than double them in length. Recently, analyses showed that several of the edited genes possess the capacity to encode two different protein products. The overlapped reading frames can be accessed through alternative RNA editing that shifts the translated reading frame. In this study, we analyzed the editing patterns of three putative dual-coding genes, ribosomal protein S12 (RPS12), the 5' editing domain of NADH dehydrogenase subunit 7 (ND7 5'), and C-rich region 3 (CR3). We found evidence that alternatively 5'-edited ND7 5' and CR3 transcripts are present in the transcriptome, providing evidence for the use of dual ORFs in these transcripts. Moreover, we found that CR3 has a complex set of editing pathways that vary substantially between cell lines. These findings suggest that alternative editing can work to introduce genetic variation in a system that selects against nucleotide mutations.

摘要

布氏锥虫具有高度复杂的 RNA 编辑系统,该系统使用向导 RNA 指导线粒体 mRNA 中尿嘧啶的插入和缺失。这些变化广泛改变了靶 mRNA,并使它们的长度增加一倍以上。最近的分析表明,几个经过编辑的基因具有编码两种不同蛋白质产物的能力。重叠的阅读框可以通过改变翻译阅读框的选择性 RNA 编辑来访问。在这项研究中,我们分析了三个假定的双编码基因的编辑模式,核糖体蛋白 S12(RPS12)、NADH 脱氢酶亚单位 7 的 5'编辑结构域(ND7 5')和富含 C 的区域 3(CR3)。我们发现了证据表明,替代的 5'编辑 ND7 5'和 CR3 转录本存在于转录组中,为这些转录本中使用双 ORF 提供了证据。此外,我们发现 CR3 具有一组复杂的编辑途径,在细胞系之间差异很大。这些发现表明,替代编辑可以在一个选择核苷酸突变的系统中引入遗传变异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/5b927b2c9a6c/gkz1131fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/c80040a3b71c/gkz1131fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/e13748260fd6/gkz1131fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/c0a9cbe50e03/gkz1131fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/c4e9ebb4105d/gkz1131fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/d73dbee3e2a3/gkz1131fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/6f5dffac2dfc/gkz1131fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/d94f96bc0ddd/gkz1131fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/492e005bf80a/gkz1131fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/5b927b2c9a6c/gkz1131fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/c80040a3b71c/gkz1131fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/e13748260fd6/gkz1131fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/c0a9cbe50e03/gkz1131fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/c4e9ebb4105d/gkz1131fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/d73dbee3e2a3/gkz1131fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/6f5dffac2dfc/gkz1131fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/d94f96bc0ddd/gkz1131fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/492e005bf80a/gkz1131fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6073/7026638/5b927b2c9a6c/gkz1131fig9.jpg

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Intrinsic and regulated properties of minimally edited trypanosome mRNAs.最小编辑的锥虫 mRNA 的固有和调节特性。
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Massive mitochondrial DNA content in diplonemid and kinetoplastid protists.原生动物双滴虫目和动基体目生物中存在大量的线粒体 DNA 含量。
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