The mystery of the molecule that reads the genetic information is solved
RIKEN scientists explain how RNA polymerase moves through nucleosomes on DNA strands
Japanese scientists at the RIKEN Biosystems Dynamics Research Center have unraveled a mystery related to gene activity in the cell nucleus. For the first time, he explained how RNA polymerase molecules, which synthesize messenger RNA, pass through the nuclear proteins that package the DNA chain without being destroyed. research results, Published In the journal Science.
In the nucleus of a eukaryotic cell, DNA is wrapped around histone proteins to form nucleosomes, the basic units of chromatin (segregated material) that resemble “beads on a string.” Nucleosomes, which each contain eight histones (an octamer), allow DNA to be packaged in a more compact form, but at the same time they are a physical barrier for the DNA-dependent RNA polymerase II enzyme, which is responsible for reading. Genetic information is stored in DNA. RNA polymerase II must pass through nucleosomes, preserving their structure, but how this happens was not known until now.
It is known that RNA polymerase II, while moving along the DNA, binds to several accessory proteins. One of them is a specific protein that facilitates chromatin transcription (FAT), which is involved in the disassembly of the nucleosome before the polymerase and promotes its reassembly behind the polymerase. This process also requires the presence of transcription factors Spt6, Spn1, Spt4/5, Elf1, TFIIS and Paf1, which contribute to the continuous function of RNA polymerase.
In the new work, the researchers visualized the passage of RNA polymerase II through the nucleosome using cryoelectron microscopy, which reveals the size of the molecules with atomic resolution. To do this, they created several DNA samples with nucleosomes, during the transcription of which the polymerase stopped at different points, where its leading edge was close to twisted sections of DNA. In total, six different conformations were visualized as a result of interactions between nucleosomes, polymerases, FACT and transcription factors.
It turns out that transcription factors cover almost the entire surface of RNA polymerase, forming a kind of nuclear factory with a tunnel through which the DNA strand passes. As this complex approaches the nucleosome, DNA unwinds and FACT and transcription factors interact with histones. When the complex approaches the center of the nucleosome, only one-third of the octamer surface is covered with DNA, then the nucleosome separates into two parts – a hexamer (six histones) and a dimer (two histones).
In the next step, FACT binds to both fragments and transfers them to the DNA strand left behind by the polymerase. First, the hexamer, and then the dimer, binds to the DNA, and as the complex progresses, it turns, causing the nucleosome to reassemble. An important role in this is played by the factors Spt4, Spt5, Spt6 and Paf1, which form a “cradle” at the DNA exit site – a structural recess where FACT associated with histones is located.
According to the authors, the results of the study will help to study the mechanisms of diseases such as cancer and to develop new treatments.
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