Decoding the grammar of transcriptional regulation from RNA polymerase measurements: models and their applications

The genomic revolution has indubitably brought about a paradigm shift in the field of molecular biology, wherein we can sequence, write and re-write genomes. In spite of achieving such feats, we still lack a quantitative understanding of how cells integrate environmental and intra-cellular signals at the promoter and accordingly regulate the production of messenger RNAs. This current state of affairs is being redressed by recent experimental breakthroughs which enable the counting of RNA polymerase molecules (or the corresponding nascent RNAs) engaged in the process of transcribing a gene at the single-cell level. Theorists, in conjunction, have sought to unravel the grammar of transcriptional regulation by harnessing the various statistical properties of these measurements. In this review, we focus on the recent progress in developing falsifiable models of transcription that aim to connect the molecular mechanisms of transcription to single-cell polymerase measurements. We discuss studies where the application of such models to the experimental data have led to novel mechanistic insights into the process of transcriptional regulation. Such interplay between theory and experiments will likely contribute towards the exciting journey of unfurling the governing principles of transcriptional regulation ranging from bacteria to higher organisms.