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Actinomycetes are known for their ability to produce rich variety of natural products, and particularly, polyketides. Many of the genes that encode the biosynthetic pathways are pretty big, as they could reach 20kb. These bacteria most probably have some kind of mechanism that would ensure efficient transcription and translation of these long ORFs. This could be done in two ways: either by stablizing the mRNA:RNA polymerase complex, or by stabilizing the mRNA:ribosome complex. Have any of you heard of such mechanisms in bacteria?

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  • $\begingroup$ What makes you think this is so? Where did you read it? There is a specific mechanism for termination of translation and release of ribosome subunits. I may be wrong but I see no reason that ribosomes would fall off long mRNAs. $\endgroup$ – David Apr 6 '16 at 21:44
  • $\begingroup$ A professor I talked to at a conference mentioned it, so I know they exist, I just don't know how they are called. And it definitely makes sense for them to exist, since these ORFs are so long. $\endgroup$ – Gergana Vandova Apr 6 '16 at 21:48
  • $\begingroup$ Don't believe everything you hear from professors. And don't be so definite about your logical rectitude. Does the RNA polymerase need extra proteins so it doesn't fall off the DNA when transcribing longer genes? $\endgroup$ – David Apr 6 '16 at 22:01
  • $\begingroup$ I am not saying they exist 100%. I am just saying that it makes sense. $\endgroup$ – Gergana Vandova Apr 6 '16 at 22:07
  • $\begingroup$ To me it raises as many questions as it answers. For example how do these proteins distinguish short from long mRNAs? $\endgroup$ – David Apr 6 '16 at 22:14
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I have searched for information on this topic as I used to work in the area of protein biosynthesis, but without success. However one argument against there being a tendency for ribosomes to fall off mRNA is the very specific mechanism for ribosome release after the stop codon has been reached (described here).

There are other possible problems with very long mRNAs:

  • Possible degradation of (prokaryotic) mRNA during a long translation time. I would imagine that the mRNA would have to contain structural features that prolonged its life.
  • Possible misfolding and precipitation of the protein product before the whole protein is completed. I think there are probably chaperone proteins that protect hydrophobic regions or encourage folding of domains to prevent this.

As a footnote, the longest mRNA is thought to be that for the muscle protein, titin. The assembly of that on the sarcomere would not be typical of polyketides, say, but other problems encountered might be similar.

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There is indeed a gene, called nusG which is believed to be antiterminator of RNA transcription. NusG binds to RNA polymerase which leads to increased RNA elongation rate, decreased time in which the polymerase is into short-lived paused states, and suppressed long-lived stabilized pause states 1.

NusG has been shown to be important for natural product discovery and biosynthesis:

Overexpression of nusG in C. cellulolyticum enabled the isolation of seven novel analogues of closthioamide, named closthioamides B–H86. These new compounds are truncated and partially O-substituted derivatives of the antibacterial parent hexathioamide compound, but have substantially lower antibacterial activity 2

Furthermore, nusG-like gene is found in the Myxococcus xanthus gene cluster eccoding myxovirescin (TA) antibiotic. One of the polyketide-encoding genes in this cluster is ~27kb long [3]:

enter image description here

  1. Herbert, K. M. et al. E. coli NusG inhibits backtracking and accelerates pause-free transcription by promoting forward translocation of RNA polymerase. J. Mol. Biol. 399, 17–30 (2010)

  2. Peter J. Rutledge & Gregory L. Challis. Discovery of microbial natural products by activation of silent biosynthetic gene clusters. Nature Reviews Microbiology 13, 509–523 (2015)

  3. http://mibig.secondarymetabolites.org/repository/BGC0001025/index.html#cluster-1

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