Functional unknomics: Systematic screening of conserved genes of unknown function.

IF 7.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY PLoS Biology Pub Date : 2023-08-08 eCollection Date: 2023-08-01 DOI:10.1371/journal.pbio.3002222
João J Rocha, Satish Arcot Jayaram, Tim J Stevens, Nadine Muschalik, Rajen D Shah, Sahar Emran, Cristina Robles, Matthew Freeman, Sean Munro
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Abstract

The human genome encodes approximately 20,000 proteins, many still uncharacterised. It has become clear that scientific research tends to focus on well-studied proteins, leading to a concern that poorly understood genes are unjustifiably neglected. To address this, we have developed a publicly available and customisable "Unknome database" that ranks proteins based on how little is known about them. We applied RNA interference (RNAi) in Drosophila to 260 unknown genes that are conserved between flies and humans. Knockdown of some genes resulted in loss of viability, and functional screening of the rest revealed hits for fertility, development, locomotion, protein quality control, and resilience to stress. CRISPR/Cas9 gene disruption validated a component of Notch signalling and 2 genes contributing to male fertility. Our work illustrates the importance of poorly understood genes, provides a resource to accelerate future research, and highlights a need to support database curation to ensure that misannotation does not erode our awareness of our own ignorance.

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功能未知基因组学:对功能未知的保守基因进行系统筛选。
人类基因组编码了约 20,000 种蛋白质,其中许多仍未定性。显而易见的是,科学研究往往集中在研究透彻的蛋白质上,导致人们担心了解不多的基因被无端忽视。为了解决这个问题,我们开发了一个公开的、可定制的 "Unknome 数据库",该数据库根据蛋白质的未知程度对其进行排序。我们在果蝇中应用 RNA 干扰(RNAi)技术,研究了 260 个在果蝇和人类之间保守的未知基因。敲除一些基因会导致果蝇丧失生存能力,而对其余基因进行功能筛选后,我们发现了一些与果蝇生育、发育、运动、蛋白质质量控制和抗压能力有关的基因。CRISPR/Cas9基因干扰验证了Notch信号的一个组成部分和两个有助于雄性生育能力的基因。我们的工作说明了不为人们所了解的基因的重要性,为加速未来的研究提供了资源,并强调了支持数据库整理的必要性,以确保错误注释不会侵蚀我们对自身无知的认识。
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来源期刊
PLoS Biology
PLoS Biology 生物-生化与分子生物学
CiteScore
14.40
自引率
2.00%
发文量
359
审稿时长
3 months
期刊介绍: PLOS Biology is an open-access, peer-reviewed general biology journal published by PLOS, a nonprofit organization of scientists and physicians dedicated to making the world's scientific and medical literature freely accessible. The journal publishes new articles online weekly, with issues compiled and published monthly. ISSN Numbers: eISSN: 1545-7885 ISSN: 1544-9173
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