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New discoveries about the disruption of condensations in the neurodevelopmental disorder Rett syndrome provide insights into how cells share chromosomes and new opportunities for treatment. For many years, scientists have understood the cell as a more free-flowing space, where molecules float freely without the organization provided by specific cellular structures, eventually ending up in their proper place. However, in recent years, scientists have discovered that cells are more organized than previously thought, thanks to a phase-separation mechanism that occurs in cells that separates certain molecules inside the droplet from the rest. Droplets called condensates of the cell are continuous and concentrate the molecules in a specific place and improve the efficiency of certain cellular functions. Whitehead Institute Fellow Richard Young, also a professor of biology at the Massachusetts Institute of Technology (MIT), studies the unknown role that condensates play in assembling the molecules needed for gene transcription the reading of DNA into RNA.
To better understand when and how cells use phase separation executive database Charles Lee, a graduate student in Young's lab, aims to find more proteins that can form condensates. That research led to MeCP2, a protein associated with the severe neurodevelopmental disorder Rett syndrome, said Young's colleague at the Whitehead Institute, founding member Rudolf Jaenisch, The discovery of MeCP2's ability to form a condensate led to a promising collaboration between the Young and Jaenish laboratories. Two labs led by co-authors Lee and Eliot Coffey, another graduate student in Young's lab, investigated MeCP2 and whether impaired ability to form condensate contributes to Rett syndrome. During the study, the researchers also discovered how cells can use the condensates to organize the active and inactive parts of chromosomes. The findings, published June 22 in the journal Nature , report on these insights and suggest new ways to develop treatments for Rett syndrome.
Proteins that form condensates often contain intrinsically disordered regions (IDRs), long spaghetti-like strands that form a dynamic mesh. Research has historically focused on structural regions of proteins that specifically bind to other molecules, while IDRs have often been ignored. In this case, MeCP2's large IDRs were what attracted Li. "What struck me was that this protein had been studied for decades, and there were many functions for the whole protein, but there was one domain that binds DNA with a specific function. Behind that, the whole protein was broken down and the function of its parts was unknown," he said. The researchers found that MeCP2 used its IDRs to assemble and form condensates. They then tested many of the mutations in the MECP2 gene associated with Rett syndrome and found that all of them impair MeCP2's ability to form condensate.
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發表於 2022-8-21 11:55:14
