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Small RNAs and telomere biology

小RNA和端粒生物学

基本信息

批准号：
10534213
负责人：
SHAWN CAMERON AHMED
金额：
$ 31.1万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-07 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10534213
关键词：
Affect Age Aging Aplastic Anemia Biogenesis Biological Biological Models Biology CRISPR/Cas technology Caenorhabditis Caenorhabditis elegans Cell Proliferation Cell division DNA DNA Damage Development Disease Evolution Family Generations Genes Germ Cells Guanine Nucleotides Homologous Gene Human Knock-out Length Light Link Mammals Measures Messenger RNA Minisatellite Repeats Mitotic Nematoda Onset of illness Organism Pathway interactions Phenotype Polymerase Progeria Proteins Pulmonary Fibrosis RNA RNA-Directed DNA Polymerase Repression Ribonucleoproteins Role Signal Transduction Small Interfering RNA Small RNA Somatic Cell TERT gene Telomerase Telomere Maintenance Telomere Shortening Werner Syndrome chromosome fusion crosslink early onset experimental study knockout gene mutant nuclease overexpression protein folding repaired response telomere telomere loss tumor

项目摘要

Project Summary/Abstract Telomeres of most species are simple repetitive sequences that are maintained by de novo telomere repeat addition by the ribonucleoprotein telomerase. Small RNAs composed of perfect telomere repeats have been observed in several organisms, and these have been linked to silencing marks at telomeres and to DNA damage at telomeres. We discovered an endogenous C. elegans small RNA pathway that promotes telomere stability in the absence of telomerase. C. elegans small RNAs that are perfectly complementary to telomeric DNA are very rare, measuring 1 read per 10 million small RNAs. However, two related Caenorhabditis species C. brennerei and C. remanei have abundant telomeric small RNAs whose levels were increased by several orders of magnitude. Perfect telomeric small RNAs in all three Caenorhabditis species were strongly depleted for 5' guanine nucleotides that characterize major C. elegans small RNA species like 26G and 22G RNAs. These results suggest that telomeric small RNAs have a distinct biogenesis mechanism and that a dramatic change in their role at telomeres has recently occurred in Caenorhabditis species. We propose to study telomere biology in C. brennerei and C. remanei, in an effort to understand why telomeric small RNAs are so abundant in these species, how telomeric small RNAs are created, and what their functions are. Potentially analogous telomeric small RNAs have been observed in ciliates and mammals, and we may elucidate their biological relevance.

项目总结/摘要大多数物种的端粒是由端粒重复序列维持的简单重复序列添加的核糖核蛋白端粒酶。由完美的端粒重复序列组成的小RNA已经被发现，在几种生物中观察到，这些都与端粒和DNA上的沉默标记有关。端粒损伤我们发现了一个内源性的C。一种促进端粒形成的小RNA途径在没有端粒酶的情况下稳定。C.与端粒完全互补的小RNA DNA非常罕见，每1000万个小RNA中有1个读段。然而，两个相关的小杆线虫物种 C. brennerei和C. remanei有丰富的端粒小RNA，其水平增加了几个数量级。在所有三种小杆线虫中，完美的端粒小RNA都被强烈耗尽，用于表征主要C的5 '鸟嘌呤核苷酸。线虫小RNA种类如26G和22G RNA。这些结果表明，端粒小RNA具有独特的生物发生机制，最近在小杆线虫物种中发生了它们在端粒中的作用的变化。我们建议研究端粒生物学研究brennerei和C. remanei，在努力了解为什么端粒小RNA是如此端粒小RNA是如何产生的，以及它们的功能是什么。潜在在纤毛虫和哺乳动物中已经观察到类似的端粒小RNA，我们可以阐明它们的生物相关性。