National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India.
SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India.
EMBO J. 2024 Nov;43(21):5186-5210. doi: 10.1038/s44318-024-00225-y. Epub 2024 Sep 16.
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.
转录因子（TFs）通过其 DNA 结合域与 DNA 以不同强度结合来调节基因表达。此外，一些 TF 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 结合是否会导致转录的差异仍不清楚。在这项研究中，我们证明了雌激素受体α（ERα），一种配体激活的 TF，以配体依赖的方式与 RNA 相互作用。RNA 结合缺陷导致 ERα 募集的全基因组丧失，尤其是在较弱的 ERα 基序处。此外，在缺乏 RNA 结合能力的情况下，ERα 在核内的流动性增加。出乎意料的是，这种流动性的增加与聚合酶大量加载和具有低强度基序的 ERα 调节基因的转录相吻合。然而，ERα 在染色质上的高稳定结合会对配体依赖性转录产生负面影响。总的来说，我们的结果表明，RNA 相互作用将 ERα 在低亲和力位点上进行空间限制，以精细调节基因转录。
