Biogenesis of mRNA-derived telomerase long noncoding RNA

mRNA 衍生端粒酶长非编码 RNA 的生物发生

• 批准号: 10638429
• 负责人: Julian J-L Chen
• 金额: $ 30.25万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-16 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10638429
• 关键词: 3' Untranslated Regions; Alternative Splicing; Amino Acid Sequence; Animals; Ascomycota; Basidiomycota; Binding Proteins; Biogenesis; Biology; CRISPR/Cas technology; Cell physiology; Chromosomal Stability; Code; Complex; DNA; Enzymes; Eukaryota; Evolution; Family; Genes; Genetic; Genetic Transcription; Genome Stability; Goals; Introns; Life Cycle Stages; Mammalian Cell; Measures; Messenger RNA; Molecular; Nucleotides; Outcome; Pathway interactions; Pattern; Plants; Play; Process; Protein Isoforms; Proteins; RNA; RNA Decay; RNA Polymerase II; RNA Polymerase III; RNA Precursors; RNA Processing; RNA Splicing; RNA metabolism; RNA-Binding Proteins; Regulation; Research; Ribonucleoproteins; Role; Small Nuclear RNA; Small Nucleolar RNA; Structure; Technology; Telomerase; Telomerase RNA Component; Telomere Maintenance; Transcript; Untranslated RNA; Ustilago; Yeasts; cancer cell; fungus; genetic information; human disease; innovative technologies; insight; mRNA Precursor; model organism; nanopore; novel; nuclease; posttranscriptional; programs; protein expression; sequencing platform; stem cells; tool

Project Summary Most RNA molecules transcribed in mammalian cells do not encode for protein sequences. Among these noncoding RNAs (ncRNA) is a vast family of long noncoding RNAs (lncRNAs) that are larger than 200 nt. LncRNAs can modulate cellular protein expression patterns by influencing the transcription of many genes, the post-transcriptional fate of mRNAs and ncRNAs, and the turnover and localization of proteins. Telomerase RNA is a unique class of lncRNA that functions as an integral component of the telomerase ribonucleoprotein complex which maintains genomic stability and cellular immortality in cancer and stem cells. The overarching goal of this project is to understand the mechanism and regulation of a novel mRNA-derived biogenesis of telomerase RNA (lncRNA) in Ustilago maydis, a basidiomycete fungus. Telomerase RNA in Ascomycete yeasts and animals, telomerase RNAs are transcribed by RNA polymerase II and share biogenesis pathways with small nuclear RNA (snRNA) and box H/ACA small nucleolar RNA (snoRNA), respectively. In contrast, telomerase RNAs in ciliates and plants are transcribed by RNA polymerase III. These distinct biogenesis mechanisms employed by these homologous telomerase RNA molecules from different eukaryotic kingdoms or groups provide unparalleled opportunities for understanding the fundamental principles underlying the biogenesis and evolution of the vast varieties of noncoding RNA species in biology. We have recently identified the first Basidiomycete telomerase RNA from U. maydis, a fungal model organism. Animal and yeast TRs are transcribed by RNA polymerase II with a protective cap at the 5’-end. intriguingly, the U. maydis TR lacks a protective 5’ cap and is processed from the 3’-untranslated region of a protein-coding mRNA precursor. In this research program, we will identify determinants in the TR precursor that regulate the biogenesis of the mature U. maydis TR from the protein-coding mRNA. We will also study the function and expression of the protein encoded in the mRNA precursor. Lastly, we will identify telomerase accessory proteins in U. maydis and determine their roles in regulating the U. maydis TR biogenesis. Successful outcomes of these specific aims will provide comprehensive and exciting details needed for understanding the unprecedented mRNA-derived biogenesis mechanism of telomerase lncRNA.

项目摘要 在哺乳动物细胞中转录的大多数RNA分子都不编码蛋白质序列。其中 非编码RNA（NCRNA）是一个大于200 nt的长期非编码RNA（LNCRNA）的庞大家族。 LNCRNA可以通过影响许多基因的转录，即 mRNA和NCRNA的转录后命运，以及蛋白质的周转和定位。端粒酶 RNA是一类独特的lncRNA，它是端粒酶蛋白的组成部分的功能 维持癌症和干细胞中基因组稳定性和细胞永生的复合物。总体 该项目的目标是了解新型mRNA衍生的生物发生的机制和调节 Ustilago Maydis的端粒酶RNA（LNCRNA），一种碱性真菌。 端粒酶RNA在子宫菌酵母和动物中，端粒酶RNA由RNA转录 聚合酶II并用小核RNA（SNRNA）和盒子H/ACA共享生物发生途径 核仁RNA（SNORNA）。相反，纤毛和植物中的端粒酶RNA被转录 RNA聚合酶III。这些同源端粒酶RNA携带的这些独特的生物发生机制 来自不同真核王国或群体的分子为理解提供了无与伦比的机会 非编码RNA的大量生物发生和演变的基本原理 生物学物种。 我们最近确定了来自U. Maydis的第一个基本型端粒酶RNA，一种真菌模型 生物。动物和酵母TR由RNA聚合酶II转录，并在5'末端具有保护帽。 有趣的是，美国Maydis TR缺乏受保护的5'盖，并从A的3英寸未翻译区域进行处理 蛋白质编码mRNA前体。在该研究计划中，我们将确定tr前体中的确定词 从蛋白质编码mRNA中调节成熟的U. Maydis TR的生物发生。我们还将研究 在mRNA前体中编码的蛋白质的功能和表达。最后，我们将确定端粒酶 U. Maydis的辅助蛋白，并确定其在调节美国Maydis TR生物发生中的作用。 这些特定目标的成功结果将为需要提供全面而令人兴奋的细节 了解端粒酶lncRNA的前所未有的mRNA衍生的生物发生机制。