Genetic information is encoded in the nucleotide sequence of the DNA. This
sequence contains the instruction code of the cell - determining protein
structure and function, and hence cell function and fate.
Transcription is a vital stage in the process of gene expression and a
major contributor to fluctuations in gene expression levels. It is
typically modelled as a single step process with Poisson statistics.
However, recent single molecule experiments
raise questions about the validity of such a simple single step picture.
I will present a molecular multi-step model of transcription elongation
that demonstrates that transcription times are in general
non-Poisson distributed. In particular, we model transcriptional
pauses due to backtracking of the RNA polymerase as a first passage
process. When transcriptional pauses result in long transcription
times, I will demonstrate that this naturally leads to bursts of mRNA
production and non-Poisson statistics of mRNA levels.
The viability and endurance of organisms crucially depend on the fidelity
with which genetic information is transcribed/translated (during mRNA and
protein production) and replicated (during DNA replication). However,
thermodynamics introduces significant fluctuations which would incur large
error rates if efficient proofreading mechanisms were not in place. I will
examine a putative mechanism for error correction during DNA
transcription, which relies on backtracking of the RNA polymerase (RNAP).
This model will be used to calculate the error fraction as a function of
the relevant rates (translocation, cleavage, backtracking and