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This is quite a specific question, and I'm hoping someone might be able to assist in a literature hunt I've been engaged in for ages.

I study some long bacterial operons, and have noticed that the GC% content at the 3' end drops significantly compared to the beginning of the operon.

I vaguely recall hearing (I can't remember if it was from a paper or a lecture or something), that lower GC (higher AT) content can promote transcription. This sounds plausible to me since it promotes strand separation (this is how replicon origins are often defined), but I've tried several times to find a paper that might demonstrate/attest to this. The hypothesis therefore, is that the distal ends of the operon might have lower GC in order to enhance transcription as the influence of the 5' UTR promotor sequences etc being to wane over a distance.

Has anyone ever come across such a paper or has any information to confirm or deny this? Information to the contrary (e.g. high GC reduces transcription) would also suffice.

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  • $\begingroup$ Why would you think that transcription would be controlled at the 3' end of an operon? Surely all that it could do there is help termination. I don't understand what you mean in molecular terms about the influence of the promotor sequences begining (?) to wane. The promotor promotes binding of RNA polymerase, that's all. And the promotor sequences are not part of the 5'UTR (untranslated region of the mRNA) as they are not transcribed into mRNA. Have you compared different operons in your bacterium? The problem with GC content is that this varies drastically among bacteria. $\endgroup$ – David May 22 '18 at 19:38
  • $\begingroup$ What makes you think that bacteria do not modulate transcription along the transcript? The influence of a promoter sequence is essentially strongest nearest to it due to the processivity (or lack of) of the RNA polymerase. Yes I have compared multiple equivalent operant across various related bacteria and this is a consistent trend. I believe it has some significance as bacteria have mechanisms such as transcript elongation to assist in transcribing very long sequences. That is, at least, my conjecture. I am positive I’ve heard of this as a phenomenon before now... $\endgroup$ – Joe Healey May 22 '18 at 20:38
  • $\begingroup$ Now you mention it I have heard that there was a problem with reading long sequences, although whether this was transcription or translation I don't remember and can't find it. But I would be wary of the simplistic GC = stronger base pairing therefore more difficult to separate idea. There was expectation that thermophillic bacteria would have higher GC contents, but they don't, and high-GC genomes like those of the herpes simplex virus manage as well as the related low-GC varicella zosta. $\endgroup$ – David May 22 '18 at 21:31
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This paper suggests the opposite in mammalian cells. Obviously, gene regulation is quite different in prokaryotes, so don't know how much confidence you want to put into that one.

This paper suggests more of the same, but includes some caveats related to prokaryotes that may pique your interest. They do a pretty in-depth dive of GC content near genes from many different species, but I haven't read it closely enough to give a good breakdown.

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