Nascent RNA kinetics with complex promoter architecture: Analytic results and parameter inference

Abstract

Transcription is a stochastic process that involves several downstream operations, which make it difficult to model and infer transcription kinetics from mature RNA numbers in individual cell. However, recent advances in single-cell technologies have enabled a more precise measurement of the fluctuations of nascent RNA that closely reflect transcription kinetics. In this paper, we introduce a general stochastic model to mimic nascent RNA kinetics with complex promoter architecture. We derive the exact distribution and moments of nascent RNA using queuing theory techniques, which provide valuable insights into the effect of the molecular memory created by the multistep activation and deactivation on the stochastic kinetics of nascent RNA. Moreover, based on the analytical results, we develop a statistical method to infer the promoter memory from stationary nascent RNA distributions. Data analysis of synthetic data and a realistic example, the HIV-1 gene, verifies the validity of this inference method.