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S C I E N T I F I C H I G H L I G H T S

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Structural insights into RNA- mediated transcription regulation in bacteria

Transcription of RNA from DNA is tightly controlled. Using cryo-electron microscopy, molecular models of RNA polymerase regulated by the transcript itself instead of by other proteins were determined. These studies shed light on regulatory RNA elements promoting or terminating their own synthesis.

Nucleic acids come in two flavours: DNA encodes the genetic blueprint and RNA serves as a labile copy. In addition, RNA has many other regulatory and catalytic roles. Transcription is the first step to express genetic

information, where RNA is transcribed from a DNA template by RNA polymerase (RNAP). This process is highly regulated, and the underlying mechanism is conserved from bacteria to human. It goes through three phases: i) RNAP binds DNA and initiates RNA synthesis; ii) RNAP synthesises RNA directed by the DNA template; and iii) RNAP responds to a termination signal, releases the RNA transcript and dissociates from DNA.

A vast number of protein transcription factors modulate RNAP during transcription. However, a potentially more ancient and less well-understood mechanism is the regulation of RNAP by the RNA transcript itself, as opposed to the regulation by auxiliary protein factors. For example, so-called intrinsic terminators consist of a short, U-rich

Fig. 42: a) Single-particle cryo-EM reconstruction of RNA polymerase trapped at a pause site and transcribing a regulatory RNA, which promotes its own synthesis, provides novel insights into the regulatory versatility of RNA. The regulatory RNA (red) folds into a complex

structure, binds the surface of RNA polymerase and favours the active conformation of RNA polymerase. It suppresses pausing and stimulates its own synthesis. b) In absence of the regulatory RNA, RNAP could be visualised for the first time after transcript release

occurred but before dissociation from the DNA (green and purple).

stabilising interactions. Thanks to the ability to visualise what is happening in the core of the structures of moving

proteins, it is possible to gain insights into how very small alterations can be the cause of many diseases.

PRINCIPAL PUBLICATION AND AUTHORS

Visualizing protein breathing motions associated with aromatic ring flipping, L. Mariño Pérez (a), F.S. Ielasi (b), L.M. Bessa (a), D. Maurin (a), J. Kragelj (a), M. Blackledge (a), N. Salvi (a), G. Bouvignies (c), A. Palencia (b), M.R. Jensen (a), Nature 602, 695-700 (2022); https:/doi.org/10.1038/s41586-022-04417-6 (a) Institut de Biologie Structurale, Université Grenoble Alpes, CEA, CNRS, Grenoble (France) (b) Structural Biology of Novel Targets in Human Diseases, Institute for Advanced Biosciences, Université Grenoble Alpes, INSERM, CNRS, Grenoble (France) (c) École Normale Supérieure (ENS), PSL University, Sorbonne Université, CNRS, Paris (France)