Genome complexity: DNA transcription and translation II (Introduction)

by David Turell , Friday, September 11, 2020, 21:00 (1322 days ago) @ David Turell
edited by David Turell, Friday, September 11, 2020, 21:13

A repeat due to the website acting up

The transcription and translation of DNA code is highly complex and tightly controlled:

https://science.sciencemag.org/content/369/6509/1335.2?utm_campaign=twis_sci_2020-09-10...

In bacteria, the rate of transcription of messenger RNA (mRNA) by RNA polymerase (RNAP) is coordinated with the rate of translation by the first ribosome behind RNAP on the mRNA. Two groups now present cryo–electron microscopy structures that show how two transcription elongation factors, NusG and NusA, participate in this coupling. Webster et al. found that NusG forms a bridge between RNAP and the ribosome when they are separated by mRNA. With shortened mRNA, NusG no longer links RNAP and the ribosome, but the two are oriented so that newly transcribed mRNA can enter the ribosome. Wang et al. provide further insight into the effect of mRNA length on the complex structures. They also include NusA and show that the NusG-bridged structure is stabilized by NusA.

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.

The results presented here define four structural classes of TTCs: TTC-A [the previously reported expressome; TTC-B, TTC-C, and TTC-D, and show that TTC-B has structural properties indicating that it mediates NusG-dependent, NusA-dependent transcription-translation coupling in E. coli.

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: This is certainly a very highly complex system for decoding the genome with lots of controls. Accurate results are dependent upon no errors occurring and are critical because cells are constantly reproducing themselves all through life. Life is miraculous as Paul Davies calls it in his book. I have brought up the issue of errors to give a more complete view of what God has created. I believe this is the molecular system that has to be designed. I think a more complex system of molecular controls using more chaperoning molecules would have been too cumbersome resulting in reactions that were too slow for the high speed results required in life. Any analysis will show that the error rate is very tiny, indicating to me God did His design very well. Those who magnify the errors thinking that makes God look impotent or incompetent are not taking the view of God I take.