Ubiquitylation of nucleic acids by DELTEX ubiquitin E3 ligase DTX3L.

IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Reports Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI:10.1038/s44319-024-00235-1
Kang Zhu, Chatrin Chatrin, Marcin J Suskiewicz, Vincent Aucagne, Benjamin Foster, Benedikt M Kessler, Ian Gibbs-Seymour, Dragana Ahel, Ivan Ahel
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Abstract

The recent discovery of non-proteinaceous ubiquitylation substrates broadened our understanding of this modification beyond conventional protein targets. However, the existence of additional types of substrates remains elusive. Here, we present evidence that nucleic acids can also be directly ubiquitylated via ester bond formation. DTX3L, a member of the DELTEX family E3 ubiquitin ligases, ubiquitylates DNA and RNA in vitro and that this activity is shared with DTX3, but not with the other DELTEX family members DTX1, DTX2 and DTX4. DTX3L shows preference for the 3'-terminal adenosine over other nucleotides. In addition, we demonstrate that ubiquitylation of nucleic acids is reversible by DUBs such as USP2, JOSD1 and SARS-CoV-2 PLpro. Overall, our study proposes reversible ubiquitylation of nucleic acids in vitro and discusses its potential functional implications.

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DELTEX 泛素 E3 连接酶 DTX3L 对核酸的泛素化。
最近发现的非蛋白质泛素化底物拓宽了我们对这种修饰的认识,使其超越了传统的蛋白质靶标。然而,其他类型底物的存在仍然难以捉摸。在这里,我们提出了核酸也可以通过酯键形成直接泛素化的证据。DTX3L 是 DELTEX 家族 E3 泛素连接酶的成员,它能在体外泛素化 DNA 和 RNA,而且这种活性与 DTX3 共享,但与 DELTEX 家族的其他成员 DTX1、DTX2 和 DTX4 并不共享。与其他核苷酸相比,DTX3L 对 3'-terminal adenosine 更有偏好。此外,我们还证明了核酸的泛素化是可以被 USP2、JOSD1 和 SARS-CoV-2 PLpro 等 DUBs 逆转的。总之,我们的研究提出了核酸在体外的可逆泛素化,并讨论了其潜在的功能意义。
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来源期刊
EMBO Reports
EMBO Reports 生物-生化与分子生物学
CiteScore
11.20
自引率
1.30%
发文量
267
审稿时长
1 months
期刊介绍: EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry. 
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