Small RNAs and telomere biology

项目摘要/摘要 大多数物种的端粒是简单的重复序列，由从头开始的端粒重复维持 由核糖核蛋白端粒酶加成。由完美端粒重复组成的小RNA已经被 在几种生物中观察到，这些与端粒上的沉默标记和DNA有关 端粒受损。我们发现了一种内源性线虫小RNA途径，可以促进端粒 在没有端粒酶的情况下的稳定性。线虫与端粒完全互补的小RNA DNA是非常罕见的，每1000万个小RNA中就有一个读取。然而，两个相关的线虫物种 布氏华支睾吸虫和雷曼华支睾吸虫含有丰富的端粒小RNA，其水平增加了几倍 数量级。所有三种线虫的完美端粒小RNA都被强烈耗尽 对于主要线虫小RNA物种的5‘鸟嘌呤核苷酸，如26G和22G RNA。 这些结果表明，端粒小RNA具有不同的生物发生机制，并且戏剧性的 它们在端粒上的作用最近在线虫物种中发生了变化。我们建议研究 Brennerei和C.remanei中的端粒生物学，以努力理解为什么端粒小RNA如此 在这些物种中大量存在，端粒小RNA是如何产生的，以及它们的功能是什么。潜在地 在纤毛虫和哺乳动物中也观察到了类似的端粒小RNA，我们可以解释它们的 生物相关性。

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.