真核生物rna引导的程序化DNA消除的功能和机制。

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bozhidar-Adrian Stefanov, Mariusz Nowacki
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引用次数: 0

摘要

许多真核生物,从纤毛虫到哺乳动物,在减数分裂后的繁殖过程中采用程序化的DNA消除。该过程从体细胞DNA中去除特定区域,具有广泛的功能,包括基因的不可逆沉默、性别决定、基因组保护免受转座因子或整合病毒的侵害。进化出多种机制来解释这一过程的序列选择性。在某些情况下,被淘汰的序列缺乏着丝粒,两侧有保守的序列基序,这些基序可以被指定的核酸酶特异性识别和切割。在分裂时,所有缺乏着丝粒的DNA片段在随后的有丝分裂中丢失。或者,特定的序列可以像某些纤毛虫那样被互补的小rna (sRNAs)消除。这些sRNAs能够通过piwi介导的染色质重塑子募集,随后精确定位由转座酶如PiggyBac或Tc1形成的切割复合体。在这里,我们回顾了已知的参与精确srna引导的DNA切除的细胞机制的分子相互作用,此外,我们强调了突出的知识空白。我们的重点是通过sRNAs使切割复合体精确定位的模式,以及如何控制核酸酶活性以防止脱靶切割。对这一过程的机制理解可以使新的真核生物基因组编辑工具的发展成为可能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Functions and mechanisms of eukaryotic RNA-guided programmed DNA elimination.

Many eukaryotic organisms, from ciliates to mammals, employ programmed DNA elimination during their postmeiotic reproduction. The process removes specific regions from the somatic DNA and has broad functions, including the irreversible silencing of genes, sex determination, and genome protection from transposable elements or integrating viruses. Multiple mechanisms have evolved that explain the sequence selectivity of the process. In some cases, the eliminated sequences lack centromeres and are flanked by conserved sequence motifs that are specifically recognized and cleaved by designated nucleases. Upon cleavage, all DNA fragments that lack centromeres are lost during the following mitosis. Alternatively, specific sequences can be destined for elimination by complementary small RNAs (sRNAs) as in some ciliates. These sRNAs enable a PIWI-mediated recruitment of chromatin remodelers, followed up by the precise positioning of a cleavage complex formed from a transposase like PiggyBac or Tc1. Here, we review the known molecular interplay of the cellular machinery that is involved in precise sRNA-guided DNA excision, and additionally, we highlight prominent knowledge gaps. We focus on the modes through which sRNAs enable the precise localization of the cleavage complex, and how the nuclease activity is controlled to prevent off-target cleavage. A mechanistic understanding of this process could enable the development of novel eukaryotic genome editing tools.

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来源期刊
Biochemical Society transactions
Biochemical Society transactions 生物-生化与分子生物学
CiteScore
7.80
自引率
0.00%
发文量
351
审稿时长
3-6 weeks
期刊介绍: Biochemical Society Transactions is the reviews journal of the Biochemical Society. Publishing concise reviews written by experts in the field, providing a timely snapshot of the latest developments across all areas of the molecular and cellular biosciences. Elevating our authors’ ideas and expertise, each review includes a perspectives section where authors offer comment on the latest advances, a glimpse of future challenges and highlighting the importance of associated research areas in far broader contexts.
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