AI Article Synopsis
- The eukaryotic Mediator consists of a core component (cMED) and a separate kinase module (CKM) that regulates transcription by RNA Polymerase II (Pol II), affecting both the initiation and control of gene expression.
- Recent cryo-electron microscopy studies reveal how the CKM inhibits cMED-activated transcription by binding to an unstructured region in MED13 and interfering with Pol II binding and pre-initiation complex formation.
- The positioning of CKM's MED12 component helps clarify its role in enhancing gene expression after the initiation phase, providing insights into its function alongside the core Mediator complex.
Article Abstract
The eukaryotic Mediator, comprising a large Core (cMED) and a dissociable CDK8 kinase module (CKM), regulates RNA Polymerase II (Pol II)-dependent transcription. cMED recruits Pol II and promotes pre-initiation complex (PIC) formation in a manner inhibited by the CKM, which is also implicated in post-initiation control of gene expression. Herein we report cryo-electron microscopy structures of the human complete Mediator and its CKM, which explains the basis for CKM inhibition of cMED-activated transcription. The CKM binds to cMED through an intrinsically disordered region (IDR) in MED13 and HEAT repeats in MED12. The CKM inhibits transcription by allocating its MED13 IDR to occlude binding of Pol II and MED26 to cMED and further obstructing cMED-PIC assembly through steric hindrance with TFIIH and the +1 nucleosome. Notably, MED12 binds to the cMED Hook, positioning CDK8 downstream of the transcription start site, which sheds new light on its stimulatory function in post-initiation events.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11244988 | PMC |
| http://dx.doi.org/10.1101/2024.07.01.601608 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The sensor protein VdSLN1 is involved in regulating melanin biosynthesis and pathogenicity via MAPK pathway in Verticillium dahliae.
Fungal Genet Biol
January 2025
Team of Crop Verticillium wilt, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China; Western Agricultural Research Center, Chinese Academy of Agricultural Sciences, Changji 831100, China. Electronic address:
The vascular wilt fungus Verticillium dahliae is a destructive soil-borne pathogen that causes yield loss on various economically important crops. Membrane-spanning sensor protein SLN1 have been demonstrated to contribute to virulence in varying degrees among numerous devastating fungal pathogens. However, the biological function of SLN1 in V.
View Article and Find Full Text PDFA conserved fungal Knr4/Smi1 protein is crucial for maintaining cell wall stress tolerance and host plant pathogenesis.
PLoS Pathog
January 2025
Strategic Area: Protecting Crops and the Environment, Rothamsted Research, Harpenden, Hertfordshire, United Kingdom.
Filamentous plant pathogenic fungi pose significant threats to global food security, particularly through diseases like Fusarium Head Blight (FHB) and Septoria Tritici Blotch (STB) which affects cereals. With mounting challenges in fungal control and increasing restrictions on fungicide use due to environmental concerns, there is an urgent need for innovative control strategies. Here, we present a comprehensive analysis of the stage-specific infection process of Fusarium graminearum in wheat spikes by generating a dual weighted gene co-expression network (WGCN).
View Article and Find Full Text PDFTranscriptome-Based Gene Modules and Soluble Sugar Content Analyses Reveal the Defense Response of Cotton Leaves to .
Int J Mol Sci
December 2024
The Key Laboratory of Oasis Eco-Agriculture, Agriculture College, Shihezi University, Shihezi 832000, China.
is a soil-borne phytopathogenic fungus causing destructive Verticillium wilt disease that greatly threats cotton production worldwide. The mechanism of cotton resistance to Verticillium wilt is very complex and requires further research. In this study, RNA-sequencing was used to investigate the defense responses of cotton leaves using varieties resistant (Zhongzhimian 2, or Z2) or susceptible (Xinluzao 7, or X7) to .
View Article and Find Full Text PDFEffect of Bio-Electro-Magnetic-Energy-Regulation (BEMER) Horse Therapy on Cardiopulmonary Function and Recovery Quality After Isoflurane Anesthesia in 100 Horses Subjected to Pars-Plana Vitrectomy: An Investigator-Blinded Clinical Study.
Animals (Basel)
December 2024
Hanseklinik für Pferde, Karl-Benz-Straße 5-7, 27419 Sittensen, Germany.
The use of Bio-Electro-Magnetic-Energy-Regulation (BEMER) therapy during general anesthesia has not previously been reported in horses. This randomized, investigator-blinded, placebo-controlled trial evaluates equine cardiopulmonary function and recovery quality after BEMER therapy application for 15 min in 100 horses during general anesthesia using isoflurane for pars-plana vitrectomy surgery as treatment for recurrent uveitis. Visually identical blankets were used in the two groups (1:1 ratio), one with a functional BEMER module and the other with a placebo module.
View Article and Find Full Text PDFUnderstanding kinase action requires precise quantitative measurements of their activity . In addition, the ability to capture spatial information of kinase activity is crucial to deconvolute complex signaling networks, interrogate multifaceted kinase actions, and assess drug effects or genetic perturbations. Here we developed a proteomic kinase activity sensor platform (ProKAS) for the analysis of kinase signaling using mass spectrometry.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!