NusG-Spt5 Transcription Factors: Universal, Dynamic Modulators of Gene Expression.

IF 4.7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Rachel A Mooney, Junqiao Zhu, Jason Saba, Robert Landick
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引用次数: 0

Abstract

The accurate and efficient biogenesis of RNA by cellular RNA polymerase (RNAP) requires accessory factors that regulate the initiation, elongation, and termination of transcription. Of the many discovered to date, the elongation regulator NusG-Spt5 is the only universally conserved transcription factor. With orthologs and paralogs found in all three domains of life, this ubiquity underscores their ancient and essential regulatory functions. NusG-Spt5 proteins evolved to maintain a similar binding interface to RNAP through contacts of the NusG N-terminal domain (NGN) that bridge the main DNA-binding cleft. We propose that varying strength of these contacts, modulated by tethering interactions, either decrease transcriptional pausing by smoothing the rugged thermodynamic landscape of transcript elongation or enhance pausing, depending on which conformation of RNAP is stabilized by NGN contacts. NusG-Spt5 contains one (in bacteria and archaea) or more (in eukaryotes) C-terminal domains that use a KOW fold to contact diverse targets, tether the NGN, and control RNA biogenesis. Recent work highlights these diverse functions in different organisms. Some bacteria contain multiple specialized NusG paralogs that regulate subsets of operons via sequence-specific targeting, controlling production of antibiotics, toxins, or capsule proteins. Despite their common origin, NusG orthologs can differ in their target selection, interacting partners, and effects on RNA synthesis. We describe the current understanding of NusG-Spt5 structure, interactions with RNAP and other regulators, and cellular functions including significant recent progress from genome-wide analyses, single-molecule visualization, and cryo-EM. The recent findings highlight the remarkable diversity of function among these structurally conserved proteins.

NusG-Spt5 转录因子:基因表达的通用动态调节因子
细胞 RNA 聚合酶(RNAP)准确而高效地生物合成 RNA 需要辅助因子来调节转录的启动、延伸和终止。在迄今发现的众多转录因子中,延伸调节因子 NusG-Spt5 是唯一一种普遍保守的转录因子。在生命的所有三个领域都发现了其直系同源物和旁系同源物,这种普遍性强调了它们古老而重要的调控功能。NusG-Spt5 蛋白在进化过程中通过 NusG N 端结构域(NGN)的接触保持了与 RNAP 相似的结合界面,NGN 在主要的 DNA 结合裂隙之间架起了桥梁。我们认为,这些接触的不同强度受系链相互作用的调节,要么通过平滑转录本伸长的崎岖热力学景观来减少转录暂停,要么根据 NGN 接触所稳定的 RNAP 构象来增强暂停。NusG-Spt5 包含一个(在细菌和古生菌中)或多个(在真核生物中)C-末端结构域,这些结构域利用 KOW 折叠来接触不同的靶标、拴系 NGN 并控制 RNA 的生物发生。最近的研究突显了不同生物体的这些不同功能。一些细菌含有多个特化的 NusG 旁系亲属,它们通过序列特异性靶向调节操作子子集,控制抗生素、毒素或囊蛋白的产生。尽管 NusG 同源物具有共同的起源,但它们在靶标选择、相互作用伙伴以及对 RNA 合成的影响方面可能存在差异。我们描述了目前对 NusG-Spt5 结构、与 RNAP 和其他调控因子的相互作用以及细胞功能的理解,包括最近在全基因组分析、单分子可视化和低温电子显微镜方面取得的重大进展。最近的研究结果突显了这些结构上保守的蛋白质在功能上的显著多样性。
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来源期刊
Journal of Molecular Biology
Journal of Molecular Biology 生物-生化与分子生物学
CiteScore
11.30
自引率
1.80%
发文量
412
审稿时长
28 days
期刊介绍: Journal of Molecular Biology (JMB) provides high quality, comprehensive and broad coverage in all areas of molecular biology. The journal publishes original scientific research papers that provide mechanistic and functional insights and report a significant advance to the field. The journal encourages the submission of multidisciplinary studies that use complementary experimental and computational approaches to address challenging biological questions. Research areas include but are not limited to: Biomolecular interactions, signaling networks, systems biology; Cell cycle, cell growth, cell differentiation; Cell death, autophagy; Cell signaling and regulation; Chemical biology; Computational biology, in combination with experimental studies; DNA replication, repair, and recombination; Development, regenerative biology, mechanistic and functional studies of stem cells; Epigenetics, chromatin structure and function; Gene expression; Membrane processes, cell surface proteins and cell-cell interactions; Methodological advances, both experimental and theoretical, including databases; Microbiology, virology, and interactions with the host or environment; Microbiota mechanistic and functional studies; Nuclear organization; Post-translational modifications, proteomics; Processing and function of biologically important macromolecules and complexes; Molecular basis of disease; RNA processing, structure and functions of non-coding RNAs, transcription; Sorting, spatiotemporal organization, trafficking; Structural biology; Synthetic biology; Translation, protein folding, chaperones, protein degradation and quality control.
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