Molecular analysis of the mechanisms linking co-transcriptional RNA processing with chromatin silencing

共转录 RNA 加工与染色质沉默联系机制的分子分析

• 批准号: BB/G01406X/1
• 负责人: Caroline Dean
• 金额: $ 76.53万
• 依托单位: John Innes Centre
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG01406X%2F1
• 关键词: Molecular; analysis; mechanisms; linking; co

We have been studying the molecular pathways controlling flowering time in plants and this has led us into the study of a particular pathway, the autonomous pathway, which accelerates flowering by repressing a specific gene encoding a floral repressor. This pathway turns out to regulate many targets in the nucleus and not just genes regulating flowering time. A component of the autonomous pathway is a protein that binds RNA called FCA. FCA regulates the gene encoding a floral repressor, not through post-transcriptional mechanisms as suggested by its RNA-binding properties, but through a process where the transcription of the target is affected. FCA requires the activity of a second protein (FLD) that modifies the proteins (histones) intimately packaged with the DNA. We will undertake experiments to unravel how the sequence of events in gene silencing involving these proteins. This system is an excellent one to dissect a general and important question in molecular biology - how non-coding RNA drives chromatin changes. We will address how a particular RNA is selected for FCA binding and how this triggers the chromatin modification activity and thus the silencing of the locus. We will analyse one transcript in detail and then explore the generality of our findings. This work has the potential to reveal fundamental concepts important to gene regulation in many organisms.

我们一直在研究控制植物开花时间的分子途径，这使我们研究了一种特殊的途径，即自主途径，它通过抑制编码成花阻遏物的特定基因来加速开花。事实证明，这条途径调节细胞核中的许多靶点，而不仅仅是调节开花时间的基因。自主途径的一个组成部分是一种结合RNA的蛋白质，称为FCA。FCA调节编码花阻遏物的基因，不是通过其RNA结合特性所表明的转录后机制，而是通过影响靶基因转录的过程。FCA需要第二种蛋白（FLD）的活性，该蛋白修饰与DNA紧密包装的蛋白质（组蛋白）。我们将进行实验来揭示基因沉默中的事件序列如何涉及这些蛋白质。这个系统是一个很好的一个解剖在分子生物学中的一个普遍和重要的问题-非编码RNA如何驱动染色质的变化。我们将讨论如何选择特定的RNA用于FCA结合，以及这如何触发染色质修饰活性，从而沉默基因座。我们将详细分析一份成绩单，然后探讨我们发现的一般性。这项工作有可能揭示许多生物体中基因调控的重要基本概念。

项目成果

VAL1 acts as an assembly platform co-ordinating co-transcriptional repression and chromatin regulation at Arabidopsis FLC.

• DOI: 10.1038/s41467-022-32897-7
• 发表时间: 2022-09-21
• 期刊: Nature communications
• 影响因子: 16.6

Head-to-tail polymerization by VEL proteins underpins cold-induced Polycomb silencing in flowering control.

• DOI: 10.1016/j.celrep.2022.111607
• 发表时间: 2022-11-08
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Fiedler M;Franco-Echevarría E;Schulten A;Nielsen M;Rutherford TJ;Yeates A;Ahsan B;Dean C;Bienz M
• 通讯作者: Bienz M

Publisher Correction: Temperature-dependent growth contributes to long-term cold sensing.

出版商更正：温度依赖性生长有助于长期冷感。

• DOI: 10.1038/s41586-020-2694-x
• 发表时间: 2020
• 期刊: Nature
• 影响因子: 64.8
• 作者: Zhao Y

Plant vernalization proteins contain unusual PHD superdomains without histone H3 binding activity.

• DOI: 10.1016/j.jbc.2022.102540
• 发表时间: 2022-11
• 期刊: The Journal of biological chemistry
• 作者: Franco-Echevarría E;Rutherford TJ;Fiedler M;Dean C;Bienz M
• 通讯作者: Bienz M