Genome complexity: amazing dance of molecules (Introduction)

by David Turell , Friday, April 02, 2021, 14:40 (1114 days ago) @ David Turell

This study describes the assembling structure of a transcription mechanism making RNA:

https://science.sciencemag.org/content/372/6537/52.full?intcmp=trendmd-sci

"Mediating transcription
The Mediator complex is recruited by transcription factors to all protein-coding genes in eukaryotes and helps to assemble the machinery necessary to transcribe the gene. Abdella et al. present the cryo–electron microscopy structure of the human Mediator-bound preinitiation complex (Med-PIC). The structure shows how Mediator positions the long, flexible C-terminal domain of RNA polymerase II to be phosphorylated by the kinase CDK7, a crucial step for further processing of the RNA into a mature RNA. Most sites where transcription factors bind to Mediator are flexibly tethered to the complex, allowing the large Med-PIC to assemble at any gene.

"Abstract
Eukaryotic transcription requires the assembly of a multisubunit preinitiation complex (PIC) composed of RNA polymerase II (Pol II) and the general transcription factors. The coactivator Mediator is recruited by transcription factors, facilitates the assembly of the PIC, and stimulates phosphorylation of the Pol II C-terminal domain (CTD) by the TFIIH subunit CDK7. Here, we present the cryo–electron microscopy structure of the human Mediator-bound PIC at a resolution below 4 angstroms. Transcription factor binding sites within Mediator are primarily flexibly tethered to the tail module. CDK7 is stabilized by multiple contacts with Mediator. Two binding sites exist for the Pol II CTD, one between the head and middle modules of Mediator and the other in the active site of CDK7, providing structural evidence for Pol II CTD phosphorylation within the Mediator-bound PIC.

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"Here, we present the structure of the human Med-PIC assembled on a closed promoter DNA construct, with the TBP subunit of TFIID replacing the full TFIID complex. Human Mediator is held together by a central scaffold subunit, Med14, which forms two contact sites with MedTail. The precise orientation of the CAK module within Med-PIC is revealed, with clear density for the Pol II CTD in the active site. A second CTD binding site between MedHead and MedMiddle shows how Mediator positions the rest of the CTD for phosphorylation by CDK7. Many regions of Mediator that interact with transcription factors are flexibly tethered, facilitating its assembly. The structure also provides key insights into the conformational landscape of Mediator relative to the PIC."

Comment: I do not expect the reader to be able to fully understand this presentation. It requires deep training in the subject. Viewing the illustrations would help. My real point is these molecules have jobs to do and perform them as if each molecule had a mind and had memorized its function in the production line. Innate Intelligence or intelligent design? Design is obvious.