Why do RNA polymerase molecules cluster?

I received a link to a highly interesting popular article telling about the work of Ibrahim Cisse at MIT and colleagues (see this): at this time about clustering of proteins in the transcription of RNA. Similar clustering has been observed already earlier and interpreted as a phase separation Similar clustering has been observed already earlier and interpreted as a phase separation (see this). Now this interpretation is not proposed by experiments but experimenters say that it is quite possible but they cannot prove it.

I have already earlier discussed the coalescence of proteins into droplets as this kind of process in TGD framework. The basic TGD based ideas is that proteins - and biomolecules in general - are connected by flux tubes characterized by the value of Planck constant h_eff=n× h₀ for the dark particles at the flux tube. The higher the value of n is the larger the energy of given state. For instance, the binding energies of atoms decrease like 1/n². Therefore the formation of the molecular cluster liberates energy usable as metabolic energy.

Remark: h₀ is the minimal value of h_eff. The best guess is that ordinary Planck constant equals to h=6h₀ (see this and this).

TGD view about the findings

Gene control switches - such as RNA II polymerases in the DNA transcription to RNA - are found to form clusters called super-enhancers. Also so called Mediator proteins form clusters. In both cases the number of members is in the range 200-400. The clusters are stable but individual molecules spend very brief time in them. Clusers have average lifetime of 5.1±.4 seconds.

Why the clustering should take place? Why large number of these proteins are present although single one would be enough in the standard picture. In TGD framework one can imagine several explanations. One can imagine at least following reasons.

1. One explanation could relate to non-determinism of state function reduction. The transcription and its initiation should be a deterministic process at the level of single gene. Suppose that the initiation of transcription is one particular outcome of state function reduction. If there is only single RNA II polymerase, which can make only single trial, the changes to initiate the transcription are low. This would be the case if the molecule provides metabolic energy to initiate the process and becomes too "tired" to try again. In nerve pulse transmission there is analogous situation: after the passing of the nerve pulse generation the neuron has dead time period. As a matter of fact, it turns out that the analogy could be much deeper.
   

   How to achieve the initiation with certainty in this kind of situation? Suppose that the other outcomes do not affect the situation appreciabley. If one particular RNA polymerase fails to initiate it, the others can try. If the number of RNA transcriptase molecule is large enough, the transcription is bound to begin eventually! This is much like in fairy tales about princess and suitors trying to kill the dragon to get the hand of princess. Eventually the penniless swineherd enters the stage.
   
   

2. If the initiation of transcription requires large amount of metabolic energy then only some minimal number of N of RNA II polymerase molecules might be able to provide it collectively. The collective formed by N molecules could correspond to a formation of magnetic body with a large value of h_eff=n×h. The molecules would be connected by magnetic flux tubes.
   
   
3. If the rate for occurrence is determined by amplitude which is superposition of amplitudes assignable to individual proteins the the rate is proportional to N², N the number of RNA transcriptase molecules.
   

   The process in the case of cluster is indeed reported to to be suprisingly fast as compared to the expectations - something like 20 seconds. The earlier studies have suggests that single RNA polymerase stays at the DNA for minutes to hours. This would be a possible mechanism allowing to speed up bio-catalysis besides the mechanism allowing to find molecules to find by a reduction of h_eff/h= n for the bonds connecting the reactants and the associated liberation of metabolic energy allowing to kick the reactants over the potential wall hindering the reaction.
   
   

Concerning the situation before clustering there are two alternative options both relying on the model of liquid phase explaining Maxwell's rule assuming the presence of flux tube bonds in liquid and of water explaining its numerous anomalies in terms of flux tubes which can be also dark (see this).

1. Option I: Molecules could be in a phase analogous to vapour phase and there would be very few flux tube bonds between them. The phase transition would create liquid phase as flux tube loops assignable to molecules would reconnect form flux tube pairs connecting the molecules to a tensor network giving rise to quantum liquid phase. The larger then value of n, the longer the bonds between molecules would be.
   
   
2. Option I: The molecules are in the initial state connected by flux tubes and form a kind of liquid phase and the clustering reduces the value of n and therefore the lengths of flux tubes. This would liberate dark energy as metabolic energy going to the initiation of the transcription. One could indeed argue that connectedness in the initial state with large enough value of n is necessary since the protein cluster must have high enough "IQ" to perform intelligent intentional actions.
   
   

Protein blobs are said to be drawn together by the "floppy" bits (pieces) of intrinsically disorder proteins. What could this mean in the proposed picture? Disorder suggests absence of correlations between building bricks of floppy parts of the proteins.

1. Could floppiness correspond to low string tension assignable to long flux loops with large h_eff/h=n assignable to the building bricks of "floppy" pieces? Could reconnection for these loops give rise to pairs of flux tubes connecting the proteins in the transition to liquid phase? Floppiness could also make possible to scan the enviroment by flux loops for flux loops of other molecules and in case of hit (cyclotron resonance) induce reconnection.
   
   
2. In spite of floppiness in this sense, one could have quantum correlations between the internal quantum numbers of the building bricks of the floppy pieces. This would also increase the value of n serving as molecular IQ and provide molecule with higher metabolic energy liberated in the catalysis.
   
   

What about the interpretation of the time scales 5, 10, and 20 seconds? What is intriguing that so called Comorosan effect involves time scale of 5 seconds and its multiplest claimed by Comorosan long time ago to be universal time scales in bio-catalysis. This question will be considered in separate posting.

See the article Clustering of RNA polymerase molecules and Comorosan effect or the chapter Quantum Criticality and dark matter.

For a summary of earlier postings see Latest progress in TGD.

Articles and other material related to TGD.