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The Control of Gene Expression by Eukaryotic Ribonucleases

真核核糖核酸酶对基因表达的控制

基本信息

批准号：
10538638
负责人：
Guillaume F Chanfreau
金额：
$ 39.46万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2024-12-31
项目状态：
已结题

项目摘要

Project Summary/Abstract RNA degradation plays multiple essential functions in the control of gene expression. It not only regulates global transcript abundance, but also provides quality control mechanisms to eliminate improperly processed or mis-localized transcripts, or those containing premature translation termination codons (PTCs). Work in our laboratory focuses on two major RNA degradation pathways in eukaryotic cells: Nonsense- Mediated Decay (NMD), which degrades PTC-containing transcripts, and the Exosome, which processes a variety of non-coding RNAs and also degrades transcripts during quality-control processes. A combination of genomic approaches and classical genetic and biochemical analyses has allowed us to identify new roles for these pathways in gene regulation, including proofreading of splice site selection, regulation of specific mRNAs and the mechanisms underlying distinct modes of Pol.II termination. We have also identified the molecular consequences of clinical mutations in exosome subunits implicated in pontocerebellar hypoplasia (PCH). The work proposed in this application will broadly expand our understanding of the role of the subunits of the exosome and of its associated factors on RNA processing and degradation genome-wide. In addition, we will determine how the activity of the exosome is controlled during stress, and how it cooperates with other RNA quality control pathways such as those coupled to translation. Finally we will characterize the mechanisms that promote 3´-end formation for a novel class of mRNAs, which use a mechanism completely independent from the classical cleavage and polyadenylation pathway. Overall, the proposed studies will provide major advances in our understanding of the mechanisms involved in eukaryotic post-transcriptional regulations and RNA processing.

项目摘要/摘要 RNA降解在基因表达调控中起着多种重要作用。它不仅调节全球转录丰度，还提供质量控制消除未正确处理或错误本地化的记录的机制，或含有提前翻译终止密码子(PTCs)。在我们的实验室工作聚焦于真核细胞中两个主要的RNA降解途径：胡说八道- 介导的衰变(NMD)，它降解含有PTC的转录本，以及Exosome，它处理各种非编码RNA，并在质量控制流程。基因组学方法和经典遗传学的结合生化分析使我们能够确定这些途径在基因调控，包括剪接位点选择的校对、特异性的调控 MRNAs和Pol.II不同终止模式的潜在机制。我们有还确定了临床上外切体亚单位突变的分子后果与桥小脑发育不全(PCH)有关。本申请中提出的工作将广泛地扩展我们对外体亚单位作用的理解其在全基因组范围内对RNA加工和降解的相关因素。此外，我们将决定应激期间外切体的活动是如何被控制的，以及它是如何与其他RNA质量控制途径合作，例如耦合到翻译。最后，我们将描述促进3‘端形成的机制对于一类新的mRNAs，它使用一种完全独立于经典的切割和多聚腺苷酸化途径。整体而言，拟议的研究将会为我们理解真核生物所涉及的机制提供重大进展转录后调控和RNA加工。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Protocol for High-Resolution Mapping of Splicing Products and Isoforms by RT-PCR Using Fluorescently Labeled Primers.

DOI：
10.1016/j.xpro.2020.100140
发表时间：
2020-12-18
期刊：
STAR protocols
影响因子：
0
作者：
Weathers I;Gabunilas J;Samson J;Roy K;Chanfreau GF
通讯作者：
Chanfreau GF

Functional Analysis of the Zinc Finger Modules of the S. cerevisiae Splicing Factor Luc7.

酿酒酵母剪接因子 Luc7 的锌指模块的功能分析。

DOI：
10.1101/2024.02.04.578419
发表时间：
2024
期刊：
bioRxiv : the preprint server for biology
影响因子：
0
作者：
Carrocci,TuckerJ;DeMario,Samuel;He,Kevin;Zeps,NatalieJ;Harkner,CadeT;Chanfreau,Guillaume;Hoskins,AaronA
通讯作者：
Hoskins,AaronA

Robust mapping of polyadenylated and non-polyadenylated RNA 3' ends at nucleotide resolution by 3'-end sequencing.

通过 3 末端测序，以核苷酸分辨率对聚腺苷酸化和非聚腺苷酸化 RNA 3 末端进行稳健定位。