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.

项目概要/摘要大多数物种的端粒是简单的重复序列，由从头端粒重复维持由核糖核蛋白端粒酶添加。由完美端粒重复组成的小RNA 在几种生物体中观察到，这些与端粒和 DNA 的沉默标记有关端粒损伤。我们发现了一种内源性线虫小 RNA 通路，可促进端粒的形成在没有端粒酶的情况下的稳定性。线虫小RNA与端粒完全互补 DNA 非常罕见，每 1000 万个小 RNA 就有 1 个读数。然而，两个相关的秀丽隐杆线虫物种 C. brennerei 和 C. remanei 具有丰富的端粒小 RNA，其水平增加了数倍数量级。所有三种秀丽隐杆线虫物种中的完美端粒小 RNA 均被严重耗尽用于表征主要秀丽隐杆线虫小 RNA 物种（如 26G 和 22G RNA）的 5' 鸟嘌呤核苷酸。这些结果表明，端粒小RNA具有独特的生物发生机制，并且具有显着的生物发生机制。最近，在秀丽隐杆线虫属物种中，它们在端粒中的作用发生了变化。我们建议学习 C. brennerei 和 C. remanei 的端粒生物学，试图理解为什么端粒小 RNA 如此重要这些物种中丰富的端粒小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观察到类似的端粒小RNA，我们可以阐明它们的作用生物学相关性。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Telomeric small RNAs in the genus Caenorhabditis.

秀丽隐杆线虫属的端粒小RNA。

DOI：
发表时间：
2019-09
期刊：
影响因子：
0
作者：
Frenk, Stephen;Lister;Ahmed, Shawn
通讯作者：
Ahmed, Shawn

Histone deacetylase homologs regulate epigenetic inheritance of transcriptional silencing and chromosome segregation in fission yeast.

组蛋白脱乙酰酶同源物调节裂殖酵母中转录沉默和染色体分离的表观遗传。

DOI：
发表时间：
1998-10-01
期刊：
Genetics
影响因子：
3.3
作者：
S. Grewal;M. J. Bonaduce;A. J. Klar
通讯作者：
A. J. Klar

Gametes deficient for Pot1 telomere binding proteins alter levels of telomeric foci for multiple generations.

Pot1 端粒结合蛋白缺陷的配子会改变多代的端粒聚集点水平。

DOI：
发表时间：
2021-02-04
期刊：
影响因子：
5.9
作者：
Lister;Dinh, Michael;Maddox, Paul;Ahmed, Shawn
通讯作者：
Ahmed, Shawn

Germ granule dysfunction is a hallmark and mirror of Piwi mutant sterility.

胚芽颗粒功能障碍是 Piwi 突变体不育的标志和反映。

DOI：
发表时间：
2021-03-03
期刊：
影响因子：
16.6
作者：
Spichal, Maya;Heestand, Bree;Billmyre, Katherine Kretovich;Frenk, Stephen;Mello, Craig C;Ahmed, Shawn
通讯作者：
Ahmed, Shawn

Nematode chromosomes.

线虫染色体。