RNA 可微调雌激素受体-α 与低亲和性 DNA 基团的结合,从而实现转录调控。

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Journal Pub Date : 2024-11-01 Epub Date: 2024-09-16 DOI:10.1038/s44318-024-00225-y
Deepanshu Soota, Bharath Saravanan, Rajat Mann, Tripti Kharbanda, Dimple Notani
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引用次数: 0

摘要

转录因子(TF)通过其 DNA 结合域以不同强度与 DNA 结合,从而调节基因表达。此外,一些转录因子还与 RNA 相互作用,从而调节转录因子与染色质的结合。然而,RNA 介导的 TF 结合是否会导致不同的转录结果仍是未知数。在这项研究中,我们证明了雌激素受体α(ERα)是一种配体激活的TF,它以配体依赖的方式与RNA相互作用。RNA 结合缺陷会导致全基因组范围的 ERα 招募丧失,尤其是在较弱的 ERα 位点。此外,在缺乏 RNA 结合能力的情况下,ERα 在细胞核中的流动性也会增加。意想不到的是,ERα移动性增加的同时,ERα调控基因的聚合酶加载和转录能力也很强,而ERα调控基因中含有低强度的基序。然而,ERα在染色质上的高度稳定结合会对配体依赖性转录产生负面影响。总之,我们的研究结果表明,RNA相互作用在空间上将ERα限制在低亲和力位点上,以微调基因转录。
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RNA fine-tunes estrogen receptor-alpha binding on low-affinity DNA motifs for transcriptional regulation.

Transcription factors (TFs) regulate gene expression by binding with varying strengths to DNA via their DNA-binding domain. Additionally, some TFs also interact with RNA, which modulates transcription factor binding to chromatin. However, whether RNA-mediated TF binding results in differential transcriptional outcomes remains unknown. In this study, we demonstrate that estrogen receptor α (ERα), a ligand-activated TF, interacts with RNA in a ligand-dependent manner. Defects in RNA binding lead to genome-wide loss of ERα recruitment, particularly at weaker ERα-motifs. Furthermore, ERα mobility in the nucleus increases in the absence of its RNA-binding capacity. Unexpectedly, this increased mobility coincides with robust polymerase loading and transcription of ERα-regulated genes that harbor low-strength motifs. However, highly stable binding of ERα on chromatin negatively impacts ligand-dependent transcription. Collectively, our results suggest that RNA interactions spatially confine ERα on low-affinity sites to fine-tune gene transcription.

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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
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