RNA Biochemistry, University of Bayreuth, Universitätsstrasse 30, 95447, Bayreuth, Germany.
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 37673, Republic of Korea.
Nat Commun. 2022 May 4;13(1):2429. doi: 10.1038/s41467-022-29934-w.
Enhancer RNAs (eRNAs) are long non-coding RNAs that originate from enhancers. Although eRNA transcription is a canonical feature of activated enhancers, the molecular features required for eRNA function and the mechanism of how eRNAs impinge on target gene transcription have not been established. Thus, using eRNA-dependent RNA polymerase II (Pol II) pause release as a model, we here investigate the requirement of sequence, structure and length of eRNAs for their ability to stimulate Pol II pause release by detaching NELF from paused Pol II. We find eRNAs not to exert their function through common structural or sequence motifs. Instead, eRNAs that exhibit a length >200 nucleotides and that contain unpaired guanosines make multiple, allosteric contacts with NELF subunits -A and -E to trigger efficient NELF release. By revealing the molecular determinants of eRNA function, our study establishes eRNAs as an important player in Pol II pause release, and it provides new insight into the regulation of metazoan transcription.
增强子 RNA（eRNA）是起源于增强子的长非编码 RNA。虽然 eRNA 转录是激活增强子的典型特征，但 eRNA 功能所需的分子特征以及 eRNA 影响靶基因转录的机制尚未确定。因此，我们使用依赖 eRNA 的 RNA 聚合酶 II（Pol II）暂停释放作为模型，研究了 eRNA 序列、结构和长度对于它们通过从暂停的 Pol II 上分离 NELF 来刺激 Pol II 暂停释放的能力的要求。我们发现 eRNA 并不通过常见的结构或序列基序发挥其功能。相反，长度 >200 个核苷酸且包含未配对鸟苷的 eRNA 与 NELF 亚基 -A 和 -E 形成多个变构接触，从而触发有效的 NELF 释放。通过揭示 eRNA 功能的分子决定因素，我们的研究将 eRNA 确立为 Pol II 暂停释放的重要参与者，并为真核生物转录的调控提供了新的见解。
