title: Stochastic sequence-level model of coupled transcription and translation in prokaryotes.
abstract: BACKGROUND
  In prokaryotes, transcription and translation are dynamically coupled, as the latter starts before the former is complete. Also, from one transcript, several translation events occur in parallel. To study how events in transcription elongation affect translation elongation and fluctuations in protein levels, we propose a delayed stochastic model of prokaryotic transcription and translation at the nucleotide and codon level that includes the promoter open complex formation and alternative pathways to elongation, namely pausing, arrests, editing, pyrophosphorolysis, RNA polymerase traffic, and premature termination. Stepwise translation can start after the ribosome binding site is formed and accounts for variable codon translation rates, ribosome traffic, back-translocation, drop-off, and trans-translation.
  
  
  RESULTS
  First, we show that the model accurately matches measurements of sequence-dependent translation elongation dynamics. Next, we characterize the degree of coupling between fluctuations in RNA and protein levels, and its dependence on the rates of transcription and translation initiation. Finally, modeling sequence-specific transcriptional pauses, we find that these affect protein noise levels.
  
  
  CONCLUSIONS
  For parameter values within realistic intervals, transcription and translation are found to be tightly coupled in Escherichia coli, as the noise in protein levels is mostly determined by the underlying noise in RNA levels. Sequence-dependent events in transcription elongation, e.g. pauses, are found to cause tangible effects in the degree of fluctuations in protein levels.
authors.affiliation: Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, FI-33101 Tampere, Finland.
authors.forename: Jarno
authors.initials: J
authors.lastname: Mäkelä
authors.forename: Jason
authors.initials: J
authors.lastname: Lloyd-Price
authors.forename: Olli
authors.initials: O
authors.lastname: Yli-Harja
authors.forename: Andre S
authors.initials: AS
authors.lastname: Ribeiro
mesh_terms: D003062:Codon; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D008957:Models, Genetic; D014176:Protein Biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D012270:Ribosomes / Q000378:metabolism; D013269:Stochastic Processes; D014158:Transcription, Genetic
chemical_list: D003062:Codon; D012321:DNA-Directed RNA Polymerases