Publications by authors named "Subash Khadka"

Article Synopsis
  • - The eukaryotic transcriptional Mediator consists of a large core (cMED) and a dissociable kinase module (CKM), which regulates RNA polymerase II recruitment and pre-initiation complex formation
  • - Cryoelectron microscopy revealed that the CKM binds to various areas on cMED, particularly through MED12 and MED13, with MED13's disordered region blocking RNA Pol II recruitment, thus inhibiting transcription
  • - Overall, the study's findings offer insights into how the CKM represses cMED function, contributing to our understanding of the transcription regulation process in eukaryotic cells.
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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.
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Initiation and maintenance of transcriptional states are critical for controlling normal tissue homeostasis and differentiation. The cyclin dependent kinases CDK8 and CDK19 (Mediator kinases) are regulatory components of Mediator, a highly conserved complex that orchestrates enhancer-mediated transcriptional output. While Mediator kinases have been implicated in the transcription of genes necessary for development and growth, its function in mammals has not been well defined.

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This study is aimed at isolating and identifying a thermophilic cellulolytic bacterium from hot spring water and characterizing thermostable cellulase produced by the isolate. Enrichment and culture of water sample was used for isolation of bacterial strains and an isolate with highest cellulase activity was chosen for the production, partial purification, and biochemical characterization of the enzyme. Different staining techniques, enzymatic tests, and 16s ribosomal DNA (16s rDNA) gene sequencing were used for the identification of the isolate.

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Objective: To identify, in myometrial stem/progenitor cells, the presumptive cell of origin for uterine fibroids, substrates of Mediator-associated cyclin dependent kinase 8/19 (CDK8/19), which is known to be disrupted by uterine fibroid driver mutations in Mediator complex subunit 12 (MED12).

Design: Experimental study.

Setting: Academic research laboratory.

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