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CRISPR 诱导的外显子跳跃依赖于提前终止密码子突变。

CRISPR-induced exon skipping is dependent on premature termination codon mutations.

机构信息

Jilin Provincial Key Laboratory of Animal Embryo Engineering, Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, 130062, China.

Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, Guangdong, China.

出版信息

Genome Biol. 2018 Oct 17;19(1):164. doi: 10.1186/s13059-018-1532-z.

Abstract

In previous studies, CRISPR/Cas9 was shown to induce unexpected exon skipping; however, the mechanism by which this phenomenon is triggered is controversial. By analyzing 22 gene-edited rabbit lines generated using CRISPR/Cas9, we provide evidence of exon skipping at high frequency in premature termination codon-mutated rabbits but not in the rabbits with a premature termination codon mutation in exon 1 rabbits with non-frameshift or missense mutations. Our results suggest that CRISPR-mediated exon skipping depends on premature termination codon mutation-induced nonsense-associated altered splicing.

摘要

在之前的研究中,CRISPR/Cas9 被证明会诱导意外的外显子跳跃;然而,引发这种现象的机制仍存在争议。通过分析 22 条使用 CRISPR/Cas9 生成的基因编辑兔系,我们提供了证据表明,在外显子 1 中具有提前终止密码子突变的兔中以及在具有非同义或错义突变的兔中,高频发生外显子跳跃,但在具有提前终止密码子突变的兔中没有发生。我们的结果表明,CRISPR 介导的外显子跳跃取决于提前终止密码子突变诱导的无意义相关剪接改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf7/6193291/9462b31615ed/13059_2018_1532_Fig1_HTML.jpg

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