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小 RNA 指导的 DNA 消除:分子机制及其在基因组编辑中的潜力。

Small RNA-directed DNA elimination: the molecular mechanism and its potential for genome editing.

机构信息

Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.

出版信息

RNA Biol. 2021 Nov;18(11):1540-1545. doi: 10.1080/15476286.2021.1885208. Epub 2021 Feb 8.

Abstract

Transposable elements have both detrimental and beneficial effects on their host genome. is a unicellular eukaryote that deals with transposable elements in a unique way. It has a separate somatic and germline genome in two nuclei in a single cell. During sexual reproduction, a small RNA directed system compares the germline and somatic genome to identify transposable elements and related sequences. These are subsequently marked by heterochromatin and excised. In this Review, current knowledge of this system and the gaps therein are discussed. Additionally, the possibility to exploit the machinery for genome editing and its advantages over the widely used CRISPR-Cas9 system will be explored. While the bacterial derived CRISPR-Cas9 has difficulty to access eukaryotic chromatin, proteins are adept at acting in a chromatin context. Furthermore, based gene therapy in humans might be a safer alternative to Cas9 because the latter can trigger an immune response.

摘要

转座元件对其宿主基因组既有有害影响,也有有益影响。 是一种单细胞真核生物,它以独特的方式处理转座元件。它在单个细胞的两个核中有一个单独的体细胞和生殖体基因组。在有性生殖过程中,一个小的 RNA 导向系统将生殖体和体细胞基因组进行比较,以识别转座元件和相关序列。随后,这些序列被异染色质标记并切除。在这篇综述中,将讨论该系统的现有知识及其存在的空白。此外,还将探讨利用 机制进行基因组编辑的可能性及其相对于广泛使用的 CRISPR-Cas9 系统的优势。虽然源自细菌的 CRISPR-Cas9 难以进入真核染色质,但 蛋白善于在染色质环境中发挥作用。此外,基于 的人类基因治疗可能是 Cas9 的更安全替代品,因为后者会引发免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c0/8583303/09122eba48b8/KRNB_A_1885208_F0001_OC.jpg

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