Role of intrinsically disordered regions in gene expression


Recent research has highlighted the important role of intrinsically disordered regions (IDRs) in protein function and gene expression. Traditionally, proteins were thought to fold into stable 3D shapes, but about half of all proteins contain IDRs – fibrous, unstructured regions that were thought to be less important. However, a groundbreaking study published in Cell showed that IDRs are essential for chromatin regulation and gene expression.

The focus of the study was on disordered regions of the CBAF complex, a group of proteins in the nucleus that are responsible for unwinding DNA and enabling gene expression. Mutations in the IDRs of the CBAF subunits ARID1A and ARID1B, which are frequently found in cancer and neurodevelopmental disorders, disrupt chromatin remodeling and gene expression.

The researchers found that these IDRs form condensates, tiny droplets that separate from cellular fluids. These condensations allow proteins and biomolecules to assemble at specific locations for cellular activities. While the role of condensation has been established in various cellular processes, their involvement in chromatin remodeling was unknown until now.

The study examined various mutations in the IDR of the CBAF complex and their effects on the recruitment of partner proteins required for gene expression and the formation of the condensate. The findings provide insight into the mechanisms underlying these mutations and their effects on cellular processes, potentially leading to new therapeutic strategies.

This research broadens our understanding of the importance of IDRs in protein function and highlights their importance in physiology and disease. These findings have implications for therapeutic targeting of condensates and their components, and shed light on the sequence specificity and function of IDRs.

Source:
– Room. “A disorganized sector regulates CBAF activity through condensation and partner recruitment”
– Princeton University. “Protein condensations are important for the process of gene expression in cells”
– vocabulary:
– DNA: A molecule made up of two long strands of nucleotides that carry genetic instructions for growth, function, development, and reproduction.
– Acid: A substance which when dissolved in water gives a pH less than 7.0.


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