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A group of researchers from the Czech Academy of Sciences and the Baylor College of Medicine have discovered a new piece of the puzzle of how genes are expressed. The mechanism that coordinates the assembly of components inside cells that control gene expression was discovered in the journal Science. The mechanism is essential for normal cell function, but it has been implicated in cancer, neurodegeneration and HIV, and could suggest new ways to treat these conditions.
The co-corresponding author said that most previous studies focused on particular cellular components that turn genes on or off. Our work shows that the genes that regulate the rate of expression can work together to fine tune expression levels in many different settings. We found a mechanism that brings the two together and plays a role in health and disease.
The team at KU Leuven in Belgium studied the interaction between leukemia and HIV, specifically those that were caused by the N-terminal domains. The researchers found many other genes in the current study.
One of the first steps of gene expression in human cells is the machinery that regulates transcription elongation. The first author of the paper said that the process of transcription elongation is complex and involves many different proteins. The most enriched structural element in all transcription elongation factors is the TNDs. When you look for them, you will find that all the important complexes involved in transcription elongation have a TND.
The researchers believe that the docking platform for other proteins is called the TND-Interacting motifs.
Many of the segments in the Proteins lack the organization that the segments with a well-organized 3D structure have. These regions are often functional.
The authors of the paper said that the unusual behavior of the regions is remarkable. Imagine a TIM as a string that is loose at one end and moving as if it were in a storm. When it finds its partner, the string holds on tightly to the TND to keep it close. The attachment plays an important role in the early stages of gene expression.
It was exciting to see that both TIMs and TNDs bind to each other in living cells after we determined that they were bound together in a 'test tube' type of experiment. The interactions between the two are highly specific.
"I was surprised to see that IWS1 is a central player in the transcription elongation machinery and that it acts as a secondary player in the process," said Hodges, a member of the Dan L Duncan Comprehensive Cancer Center.
Veverka said that they found that IWS1 uses specific TND-TIM interactions to coordinate the activities of many transcription regulators at the same time, making it appear like a conductor at a symphony that keeps all the factors working in harmony and close by.
The team explored the consequences of disrupting a single region on the harmony of the transcription process.
Hundreds of genes with important functions were altered when we disrupted a single region. The first step of gene expression was paused and unable to be completed.
The study shows theunderappreciated role of strontium in complex biological functions. The findings can contribute to a better understanding of diseases in which these factors are disrupted. Novel targets for improved treatments for these conditions may be called TNDs and TIMs.
Katerina Cermakova and her colleagues have discovered a module that regulates transcription. www.science.org/doi/10.1126/science.abe2913
Science journal information.
The study highlights the role of disordered protein interactions in gene expression.
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