Genome complexity: transcription and translation (Introduction)

by David Turell @, Friday, September 11, 2020, 18:59 (1294 days ago) @ David Turell

This reveals the complexity:

https://science.sciencemag.org/content/369/6509/1359

Abstract
In bacteria, transcription and translation are coupled processes in which the movement of RNA polymerase (RNAP)–synthesizing messenger RNA (mRNA) is coordinated with the movement of the first ribosome-translating mRNA. Coupling is modulated by the transcription factors NusG (which is thought to bridge RNAP and the ribosome) and NusA. Here, we report cryo–electron microscopy structures of Escherichia coli transcription-translation complexes (TTCs) containing different-length mRNA spacers between RNAP and the ribosome active-center P site. Structures of TTCs containing short spacers show a state incompatible with NusG bridging and NusA binding (TTC-A, previously termed “expressome”). Structures of TTCs containing longer spacers reveal a new state compatible with NusG bridging and NusA binding (TTC-B) and reveal how NusG bridges and NusA binds. We propose that TTC-B mediates NusG- and NusA-dependent transcription-translation coupling.

Bacterial transcription and bacterial translation occur in the same cellular compartment, occur at the same time, and are coordinated processes in which the rate of transcription by the RNA polymerase (RNAP) molecule synthesizing an mRNA is coordinated with the rate of translation by the first ribosome (“lead ribosome”) translating the mRNA. Data indicate that the coordination is mediated by transcription elongation factors of the NusG/RfaH family, which contain an N-terminal domain (N) that interacts with RNAP β′ and β subunits and a flexibly tethered C-terminal domain (C) that interacts with ribosomal protein S10. These factors are thought to bridge, and thereby connect, the RNAP molecule and the lead ribosome. Further data indicate that the coordination is modulated by the transcription elongation factor NusA.

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The results presented reframe our understanding of the structural and mechanistic basis of transcription-translation coupling. The results provide high-resolution structures of the previously described expressome;TTC-A that demonstrate its incompatibility with general transcription-translation coupling. In addition, the results provide high-resolution structures of a new structural state, TTC-B, with properties assignable to general, NusG-dependent, NusA-dependent transcription-translation coupling. Our results also show that NusG stabilizes TTC-B by bridging RNAP and the ribosome 30S head, that NusA stabilizes TTC-B by bridging RNAP and the ribosome 30S body, and that NusA serves as a coupling pantograph that bridges RNAP and the ribosome 30S body in a flexible manner that allows rotation of RNAP relative to the ribosome 30S body. Finally, the results provide testable new hypotheses regarding the identities of the RNAP and NusA structural modules crucial for transcription-translation coupling (RNAP β′ ZBD and NusA KH1) and the interactions made by those structural modules (interactions with ribosomal protein S3 in the S30 head and interactions wit1h ribosomal proteins S2 and S5 in the S30 body).

Comment: If this looks highly complex, it is. Only design can create this degree of controls resulting in accurate translation and transcription. Miraculous, yet we know mistakes can happen. It depends upon your viewpoint as to how to conceive of this. Paul Davies calls life a miracle in his book about life. But some wail over the mistakes in molecular function as though they are a huge disaster and present an impotent God. It all depends on the real recognition that life functions perfectly well almost all the time. I have presented the problem of errors to demonstrate a more complete picture of the problems attendant with this mechanism of life. If each reaction had a group of mentoring/monitoring molecules to make sure each fold occurred always correctly and on time, it would have been too cumbersome to work at the speed required. Yet many mechanisms like the ones presented here have very precise controls. But keep in mind, even they can allow an error.


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