发现长链非编码rna的关键功能

IF 33.1 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Nature biotechnology Pub Date : 2024-12-11 DOI:10.1038/s41587-024-02509-4
Iris Marchal
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引用次数: 0

摘要

人类基因组包含数以千计的长链非编码rna (lncrna),其中很少与功能作用有关。尽管靶向dna的CRISPR筛选已经鉴定出功能性lncRNA,但这些筛选的特异性有限,因为基于dna的lncRNA位点的扰动也可能抑制附近的蛋白质编码基因和其他调控元件。在Cell中,Liang等人克服了这一限制。他们使用靶向rna的Cas13核酸酶开发了一种靶向lncRNA的转录组级CRISPR扰动筛选,并鉴定出具有上下文特异性或广泛必要性的778种lncRNA。作者系统地鉴定了必需的lncrna,同时评估了附近蛋白质编码基因的必要性。他们构建了一个大约75000个引导rna的文库,目标是6199个lncrna和4390个蛋白质编码转录物。比较五种人类细胞系中lncrna缺失对细胞生长的影响,揭示了共享的和细胞类型特异性的必需lncrna。在778个必需lncrna中,61%是细胞类型特异性的,33%在几个细胞系中共享,6%在所有被测试的细胞系中共享。这些普遍必需的转录本包含了先前描述过的几种lncrna,包括MALAT1和MIR17HG,以及许多新的lncrna。有趣的是,Liang等人表明,大多数必需的lncrna独立于最近的蛋白质编码基因起作用。在机制上,他们发现必需的lncrna调节细胞增殖,并在发育的早期阶段在体内高度表达。此外,必要的lncrna往往在肿瘤中差异表达,这与生存相关。这种将lncrna与功能角色联系起来的系统方法为进一步评估非编码转录本奠定了基础,这可能会导致新的治疗靶点。
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Discovering the crucial function of long noncoding RNAs
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来源期刊
Nature biotechnology
Nature biotechnology 工程技术-生物工程与应用微生物
CiteScore
63.00
自引率
1.70%
发文量
382
审稿时长
3 months
期刊介绍: Nature Biotechnology is a monthly journal that focuses on the science and business of biotechnology. It covers a wide range of topics including technology/methodology advancements in the biological, biomedical, agricultural, and environmental sciences. The journal also explores the commercial, political, ethical, legal, and societal aspects of this research. The journal serves researchers by providing peer-reviewed research papers in the field of biotechnology. It also serves the business community by delivering news about research developments. This approach ensures that both the scientific and business communities are well-informed and able to stay up-to-date on the latest advancements and opportunities in the field. Some key areas of interest in which the journal actively seeks research papers include molecular engineering of nucleic acids and proteins, molecular therapy, large-scale biology, computational biology, regenerative medicine, imaging technology, analytical biotechnology, applied immunology, food and agricultural biotechnology, and environmental biotechnology. In summary, Nature Biotechnology is a comprehensive journal that covers both the scientific and business aspects of biotechnology. It strives to provide researchers with valuable research papers and news while also delivering important scientific advancements to the business community.
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