人DDX49解旋酶新核酸酶活性的鉴定。

IF 2.9 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Royal Society Open Science Pub Date : 2024-12-18 eCollection Date: 2024-12-01 DOI:10.1098/rsos.241891

Ashley J Parkes, Sabesan Anandavijayan, Anna Lou-Hing, Olivia Downs, Tom Killelea, Louise Martin, Fiorela Kapllanaj, Edward L Bolt

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引用次数: 0

摘要

人类DDX49通过其在核核RNA加工中的重要作用而成为癌症进展和逆转录病毒疾病的新靶点。在这里，我们确定了人类DDX49的核酸酶活性，它需要在后生动物DDX49的保守区域内的活性位点天冬氨酸残基，而酵母和古细菌DDX49同源物中不存在。我们提供的证据表明，DDX49核酸酶的活性是由其解旋酶活性促进的。利用CRISPR-Cas9基因编辑技术，研究人员发现一株杂合子（DDX49 +/-） U2OS细胞系在细胞迁移方面存在缺陷，这种表型支持DDX49与癌细胞侵袭性的关联。DDX49 +/-中rna的测量表明，DDX49是维持5.8S rRNA水平所必需的。

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Identification of a novel nuclease activity in human DDX49 helicase.

Human DDX49 is an emerging target in cancer progression and retroviral diseases through its essential roles in nucleolar RNA processing. Here, we identify nuclease activity of human DDX49, which requires active site aspartate residues within a conserved region of metazoan DDX49s that is absent from yeast and archaeal DDX49 homologues. We provide evidence that DDX49 nuclease activity is facilitated by its helicase activity. Using CRISPR-Cas9 genetic editing, we show that a heterozygous (DDX49 ^+/-) U2OS cell line is defective at cell migration, a phenotype supporting the association of DDX49 with cancer cell invasiveness. Measurement of RNAs in DDX49 ^+/- indicates that DDX49 is required to sustain levels of 5.8S rRNA.

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来源期刊

Royal Society Open Science Multidisciplinary-Multidisciplinary

CiteScore

6.00

自引率

0.00%

发文量

508

审稿时长

14 weeks

期刊介绍： Royal Society Open Science is a new open journal publishing high-quality original research across the entire range of science on the basis of objective peer-review. The journal covers the entire range of science and mathematics and will allow the Society to publish all the high-quality work it receives without the usual restrictions on scope, length or impact.