Transcriptional bursts: A unified model of machines and mechanisms

Abstract

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 ...

Steady-state distributions of nascent RNA for general initiation mechanisms

“…The expression similar to the one in Eq. ( 48) was previously derived for the discrete-time TASEP with parallel [32,59] and random-sequential [60] hopping.…”

Contribution of RNA Degradation to Intrinsic and Extrinsic Noise in Gene Expression

“…Most studies have focused on how stochasticity is affected by transcription, including the control by promoters, replication, elongation, and chromatin dynamics (Huber et al, 2016;Peterson et al, 2015;Tripathi and Chowdhury, 2008;Yang et al, 2014). In addition to the above processes that affect the rate of RNA synthesis, RNA degradation is the second determinant of RNA abundance.…”

Signaling Mechanism of Transcriptional Bursting: A Technical Resolution-Independent Study

“…In individual eukaryotic cells, transcription universally occurs in episodic bursts [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. While a gene is “active”, a group of RNA polymerases successively departs from the promoter and gets into elongation, leading to the release of a number of transcripts.…”