Systematic and functional genomics of coding and non-coding transcription during gene expression regulation in yeast

酵母基因表达调控过程中编码和非编码转录的系统和功能基因组学

• 批准号: 344650877
• 负责人: Professor Dr. Michael Knop
• 金额: --
• 依托单位: Zentrum für Molekulare Biologie (ZMBH)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/344650877?language=en
• 关键词: Systematic; functional; genomics; coding; non

Cellular protein homeostasis ensures that the optimal amount of each protein is available at its site of action within an organism. This homeostasis is monitored by a series of regulatory systems - from control of gene expression and mRNA translation to protein removal via degradation pathways. Together they ensure the ideal amount of each protein in any given situation. It has become evident that the classical model of promoter-mediated gene regulation alone cannot fully explain gene expression. Rather, a number of other factors, such as transcription of overlapping non-coding RNAs, chromatin structure and genomic location, also play important roles in gene regulation. The aim of this project is to investigate the regulation of single genes comprehensively in order to quantify the contribution of each of these factors. To reach this goal, we will apply two complementary methods based on high-throughput genetics and CRISPR/Cas9 mediated genome editing. We will use baker's yeast as a model organism to explore a large number of genes, coding sequences and non-coding transcripts in the context of cellular fitness. The project will be carried out within a well-established collaboration between a genome biology / bioinformatics oriented work group at EMBL and a cell biology group at the ZMBH. The experiments we will perform aim at exploring the basic principles of gene regulation using quantitative methods.

细胞蛋白质稳态确保生物体内每种蛋白质的作用位点都有最佳数量。这种稳态由一系列调控系统监控——从基因表达和 mRNA 翻译的控制到通过降解途径去除蛋白质。它们共同确保在任何给定情况下每种蛋白质的理想含量。很明显，启动子介导的基因调控的经典模型本身并不能完全解释基因表达。相反，许多其他因素，例如重叠非编码 RNA 的转录、染色质结构和基因组位置，也在基因调控中发挥着重要作用。该项目的目的是全面研究单基因的调控，以量化每个因素的贡献。为了实现这一目标，我们将应用两种基于高通量遗传学和 CRISPR/Cas9 介导的基因组编辑的互补方法。我们将使用面包酵母作为模式生物，在细胞适应性的背景下探索大量基因、编码序列和非编码转录本。该项目将在 EMBL 的基因组生物学/生物信息学工作组和 ZMBH 的细胞生物学组之间建立良好的合作关系进行。我们将进行的实验旨在利用定量方法探索基因调控的基本原理。

项目成果

Chromatin-sensitive cryptic promoters putatively drive expression of alternative protein isoforms in yeast

染色质敏感的隐性启动子可能驱动酵母中替代蛋白质亚型的表达

• DOI: 10.1101/gr.243378.118
• 发表时间: 2019-11
• 期刊: Genome Research
• 影响因子: 7
• 作者: Wu Wei;Bianca P. Hennig;Jingwen Wang;Yujie Zhang;Ilaria Piazza;Yerma Pareja Sanchez;Christophe D. Chabbert;Sophie H. Adjalley;Lars M. Steinmetz;Vicent Pelechano
• 通讯作者: Vicent Pelechano

Rpb4 and Puf3 imprint and post-transcriptionally control the stability of a common set of mRNAs in yeast

• DOI: 10.1080/15476286.2020.1839229
• 发表时间: 2020-11-02
• 期刊: RNA BIOLOGY
• 影响因子: 4.1
• 作者: Garrido-Godino, A. I.;Gupta, I.;Navarro, F.
• 通讯作者: Navarro, F.

Gene dosage screens in yeast reveal core signalling pathways controlling heat adaptation

酵母中的基因剂量筛选揭示了控制热适应的核心信号通路

• DOI: 10.1101/2020.08.26.267674
• 发表时间: 2020
• 期刊: bioRxiv
• 作者: A. Johansson;J.D. Smith;L. Parts;L.M. Steinmetz
• 通讯作者: L.M. Steinmetz