MSGID: 1:317/3 62735300   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Gene expression in the nervous system: Mechanism for its targeted   
   stimulation discovered    
      
     Date:   
         May 4, 2022   
     Source:   
         Universita"t Bayreuth   
     Summary:   
         Genes are the carriers of our genetic information. They are read   
         in our cells and used to produce ribonucleic acids (RNAs). During   
         this process, termed transcription, the enzyme RNA polymerase   
         II has a decisive influence on the exact time at which genes are   
         read and on the intensity with which this happens. In their recent   
         article, researchers have shown exactly how RNA polymerase II is   
         activated in nerve cells, and how this stimulates gene expression,   
         the targeted use of genetic information.   
      
         Their discoveries contain valuable starting points for further   
         biomedical research.   
      
      
      
   FULL STORY   
   ==========================================================================   
   Genes are the carriers of our genetic information. They are read in   
   our cells and used to produce ribonucleic acids (RNAs). During this   
   process, termed transcription, the enzyme RNA polymerase II has a decisive   
   influence on the exact time at which genes are read and on the intensity   
   with which this happens. In their recent Nature Communications article,   
   researchers from the University of Bayreuth have shown exactly how RNA   
   polymerase II is activated in nerve cells, and how this stimulates gene   
   expression, the targeted use of genetic information. Their discoveries   
   contain valuable starting points for further biomedical research.   
      
      
   ==========================================================================   
   The new research results were obtained in close cooperation between the   
   Bayreuth research team led by Dr. Claus-D. Kuhn and partner universities   
   in South Korea and Switzerland. In the jointly discovered mechanism   
   the team found enhancer RNAs (eRNAs) to play a key role in activating   
   RNA polymerase II -- Pol II for short. Enhancer RNAs are non-coding,   
   i.e. they are RNA molecules that are not used as blueprints for protein   
   production. As the researchers were able to decipher, enhancer RNAs   
   switch on the activity of Pol II. They do so by detaching NELF (Negative   
   Elongation Factor), a large molecular complex bound to Pol II, from Pol   
   II. NELF normally blocks Pol II activity by binding to it.   
      
   However, enhancer RNAs can only act as "liberators" of Pol II under two   
   conditions: They need to have a minimum length and they need to be of a   
   characteristic molecular composition. If both these conditions are met,   
   multivalent interactions occur between the long enhancer RNAs and the   
   NELF complex, as the Bayreuth researchers discovered. This means that   
   enhancer RNAs simultaneously dock to a number of different binding sites   
   that are distributed over several subunits of NELF. Only by means of   
   these interactions are they able to detach NELF from Pol II. Enhancer   
   RNAs thereby ensure that Pol II is reactivated and resumes the process   
   of transcription following the NELF-induced paused state. "For the first   
   time, we have succeeded in demonstrating a direct mechanistic connection   
   between enhancer RNAs and the transcription process controlled by Pol II,   
   which is a key component of gene expression," says Dr.   
      
   Claus-D. Kuhn, Heisenberg Professor for RNA Biochemistry at the University   
   of Bayreuth.   
      
   The Bayreuth researchers and their cooperation partners gained their   
   new insights by studying cortical neurons in mice. As soon as these   
   neurons are stimulated by electrical stimuli, they produce large   
   amounts of enhancer RNAs for a short period of time. These non-coding   
   RNAs then activate genes that are important for nerve growth and   
   their improved interconnectivity. They achieve this by detaching   
   the NELF complex from Pol II. "To the best of our knowledge, this   
   is the first time that a direct, mechanistic link between neuronal   
   activity, enhancer transcription, and gene activation has been shown,"   
   says Bayreuth biochemist Dr. Vladyslava Gorbovytska, first author of   
   the study. "In the future, the knowledge we have gained could make   
   it possible to specifically modulate brain activity. This would be a   
   significant asset for the treatment of many neurodegenerative diseases."   
   The study, published in Nature Communications, also expands previous   
   knowledge regarding the role of enhancers, which are regulatory areas in   
   DNA. Enhancers are known to be indispensable for initiating transcription   
   in higher organisms, such as humans. This is the case as they serve   
   as binding platforms for so- called transcription factors. The research   
   conducted at the University of Bayreuth now shows that they influence gene   
   expression in yet another, universally applicable way: Enhancers are read   
   by Pol II, resulting in large amounts of enhancer RNAs. In this respect,   
   these non-coding RNAs owe their existence precisely to the enzyme that   
   they later release from a paused state and activate.   
      
      
   ==========================================================================   
   Story Source: Materials provided by Universita"t_Bayreuth. Note: Content   
   may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Vladyslava Gorbovytska, Seung-Kyoon Kim, Filiz Kuybu, Michael   
      Go"tze,   
         Dahun Um, Keunsoo Kang, Andreas Pittroff, Theresia Brennecke,   
         Lisa-Marie Schneider, Alexander Leitner, Tae-Kyung Kim,   
         Claus-D. Kuhn. Enhancer RNAs stimulate Pol II pause release by   
         harnessing multivalent interactions to NELF. Nature Communications,   
         2022; 13 (1) DOI: 10.1038/s41467-022-29934-w   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2022/05/220504110427.htm   
      
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