Department of Structural and Chemical Biology, Center for Biological Research 'Margarita Salas', CIB, CSIC, Av. Ramiro de Maeztu 9, 28040 Madrid, Spain.
Department of Biological Physical Chemistry, Institute of Physical-Chemistry 'Blas Cabrera', CSIC, C/Serrano 119, 28006 Madrid, Spain.
Biochem Soc Trans. 2023 Jun 28;51(3):1257-1269. doi: 10.1042/BST20221418.
A substantial part of living cells activity involves transcription regulation. The RNA polymerases responsible for this job need to know 'where/when' to start and stop in the genome, answers that may change throughout life and upon external stimuli. In Saccharomyces cerevisiae, RNA Pol II transcription termination can follow two different routes: the poly(A)-dependent one used for most of the mRNAs and the Nrd1/Nab3/Sen1 (NNS) pathway for non-coding RNAs (ncRNA). The NNS targets include snoRNAs and cryptic unstable transcripts (CUTs) generated by pervasive transcription. This review recapitulates the state of the art in structural biology and biophysics of the Nrd1, Nab3 and Sen1 components of the NNS complex, with special attention to their domain structures and interactions with peptide and RNA motifs, and their heterodimerization. This structural information is put into the context of the NNS termination mechanism together with possible prospects for evolution in the field.
活细胞的大部分活动都涉及转录调控。负责这项工作的 RNA 聚合酶需要知道在基因组中“何时/何地”开始和停止，这些答案可能会随着生命的变化和外部刺激而改变。在酿酒酵母中，RNA Pol II 转录终止可以遵循两种不同的途径：大多数 mRNAs 所使用的多聚（A）依赖性途径和非编码 RNA（ncRNA）的 Nrd1/Nab3/Sen1（NNS）途径。NNS 的靶标包括 snoRNAs 和由普遍转录产生的不稳定转录本（CUTs）。本综述概述了 NNS 复合物中 Nrd1、Nab3 和 Sen1 成分的结构生物学和生物物理学的最新进展，特别关注它们的结构域结构以及与肽和 RNA 基序的相互作用及其异二聚化。这些结构信息与 NNS 终止机制一起，并结合该领域的进化前景。
