RNA polymerase (RNAP) is an enzyme that synthesizes a messenger RNA (mRNA) strand which is complementary to a single-stranded DNA template. From the perspective of physicists, an RNAP is a molecular motor that utilizes chemical energy input to move along the track formed by a DNA. In many circumstances, which are described in this paper, a large number of RNAPs move simultaneously along the same track; we refer to such collective movements of the RNAPs as RNAP traffic. Here we develop a theoretical model for RNAP traffic by incorporating the steric interactions between RNAPs as well as the mechano-chemical cycle of individual RNAPs during the elongation of the mRNA. By a combination of analytical and numerical techniques, we calculate the rates of mRNA synthesis and the average density profile of the RNAPs on the DNA track. We also introduce, and compute, two new measures of fluctuations in the synthesis of RNA. Analyzing these fluctuations, we show how the level of intrinsic noise in mRNA synthesis depends on the concentrations of the RNAPs as well as on those of some of the reactants and the products of the enzymatic reactions catalyzed by RNAP. We suggest appropriate experimental systems and techniques for testing our theoretical predictions.
Polymerization of RNA from a template DNA is carried out by a molecular machine called RNA polymerase (RNAP). It also uses the template as a track on which it moves as a motor utilizing chemical energy input. The time it spends at each successive monomer of DNA is random; we derive the exact distribution of these "dwell times" in our model. The inverse of the mean dwell time satisfies a Michaelis-Menten-like equation and is also consistent with a general formula derived earlier by Fisher and Kolomeisky for molecular motors with unbranched mechano-chemical cycles. Often many RNAP motors move simultaneously on the same track. Incorporating the steric interactions among the RNAPs in our model, we also plot the three-dimensional phase diagram of our model for RNAP traffic using an extremum current hypothesis.
Transcription is the process whereby RNA molecules are polymerized by molecular machines, called RNA polymerase (RNAP), using the corresponding DNA as the template. Recent in-vivo experiments with single cells have established that transcription takes place in "bursts" or "pulses". In this letter we present a model that captures not only the mechano-chemistry of individual RNAPs and their steric interactions but also the switching of the gene between the ON and OFF states. This model accounts for the statistical properties of the transcriptional bursts. It also shows how the quantitative features of the distributions of these bursts can be tuned by controlling the appropriate steps of operation of the RNAP machines.PACS numbers: 87.16.dj; 87.18.Tt Genetic messages are encoded chemically in DNA. During gene expression this message is first transcribed into mRNA and then, from it, translated into proteins by well coordinated operation of intracellular machineries [1]. The two machines, which play key roles in transcription and translation are the RNA polymerase (RNAP) [2] and the ribosome [3,4], respectively. Each of these machines is like a mobile workshop that synthesizes a bio-polymer according to a template which also serves as the track for the movement of the workshop. Because of the probabilistic nature of the steps of gene expression, the number of mRNA and protein molecules corresponding to a single gene fluctuate randomly (see ref. [5,6,7,8,9] for reviews). It has been observed experimentally [10,11,12,13] that relatively long periods T of f of transcriptional inactivity are interspersed with brief periods T on of transcriptional "bursts". Several statistical properties of these random "bursts" (or, "pulses") have been used to characterize the temporal pattern in transcriptional events [10,11,12].Qualitatively similar bursts of transcriptional activities have been observed in both prokaryotes and eukaryotes. Some possible mechanisms of transcriptional burst have been suggested. Transcription, i.e., the process of synthesis of RNA from the corresponding DNA template, can be broadly divided into three stages, namely, initiation, elongation and termination. When the gene is switched "ON", initiation of transcription by RNAPs can take place till the gene switches back to the "OFF" state [14]. Unbinding and binding of transcription repressor molecules can give rise to such switching "ON" and "OFF" of a bacterial gene. In eukaryotic cells, chromatin remodelling enzymes can act as activators of transcription. Even if the gene does not switch OFF, burst-like transcriptional activities are possible if several RNAPs queue up behind a stalled RNAP and then, suddenly, the stalled RNAP gets reactivated [15,16]. The latter becomes very pronounced [17] when pausing is caused by backtracking of the RNAP [18].To our knowledge, the switching of the gene between the active (ON) and inactive (OFF) states is a common feature of almost all the models of transcriptional noise [19,20]. But, these models capture the en- tire ...
The semiconductor electronic industry is advancing at a very fast pace. The size of portable and handheld devices are shrinking day by day and the demand for longer battery backup is also increasing. With these requirements, the leakage power in stand-by mode becomes a critical concern for researchers. In most of these devices, memory is an integral part and its size also scales down as the device size is reduced. So, low power and high speed memory design is a prime concern. Another crucial factor is the stability of static random-access memory (SRAM) cells. This paper combines multi threshold and fingering techniques to propose a modified 6T SRAM cell which has high speed, improved stability and low leakage current in stand-by mode of the memory cell. The simulations are done using the Cadence Virtuoso tool on UMC 55 nm technology.
Molecular motors are macromolecular complexes which use some form of input energy to perform mechanical work. The filamentary tracks, on which these motors move, are made of either proteins (e.g., microtubules) or nucleic acids (DNA or RNA). Often, many such motors move simultaneously on the same track and their collective properties have superficial similarities with vehicular traffic on highways. The models we have developed provide "unified" description: in the low-density limit, a model captures the transport properties of a single motor while, at higher densities the same model accounts for the collective spatio-temporal organization of interacting motors. By drawing analogy with vehicular traffic, we have introduced novel quantities for characterizing the nature of the spatio-temporal organization of molecular motors on their tracks. We show how the traffic-like intracellular collective phenomena depend on the mechano-chemistry of the corresponding individual motors.
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