For the first time ever, a Northwestern University-led research team has peered inside a human cell to view a multi-subunit machine responsible for regulating gene expression. Called the Mediator-bound pre-initiation complex (Med-PIC), the structure is a key player in determining which genes are activated and which are suppressed. Mediator helps position the rest of the complex--RNA polymerase II and the general transcription factors--at the beginning of genes that the cell wants to transcribe. The researchers visualized the complex in high resolution using cryogenic electron microscopy (cryo-EM), enabling them to better understand how it works. Because this complex plays a role in many diseases, including cancer, neurodegenerative diseases, HIV, and metabolic disorders, researchers' new understanding of its structure could potentially be leveraged to treat disease. "This machine is so basic to every branch of modern molecular biology in the context of gene expression," said Northwestern's Yuan He (at right in photo with colleague), PhD, senior author of the study. "Visualizing the structure in 3D will help us answer basic biological questions, such as how DNA is copied to RNA." "Seeing this structure allows us to understand how it works," added Ryan Abdella, PhD student and the paper's co-first author. "It's like taking apart a common household appliance to see how everything fits together. Now we can understand how the proteins in the complex come together to perform their function." The study was published online on March 11, 2021 in Science. This marks the first time the human Mediator complex has been visualized in 3D in the human cell. The Science article is titled "Structure of the Human Mediator-Bound Transcription Pre-Initiation Complex" (https://science.sciencemag.org/content/early/2021/03/10/science.abg3074).
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