Contributions of regulated transcription and mRNA decay to the dynamics of gene expression

Abstract

Organisms have acquired sophisticated regulatory networks that control gene expression in response to cellular perturbations. Understanding of the mechanisms underlying the coordinated changes in gene expression in response to external and internal stimuli is a fundamental issue in biology. Recent advances in highthroughput technologies have enabled the measurement of diverse biological information, including gene expression levels, kinetics of gene expression, and interactions among gene expression regulatory molecules. By coupling these technologies with quantitative modeling, we can now uncover the biological roles and mechanisms of gene regulation at the system level. This review consists of two parts. First, we focus on the methods using uridine analogs that measure synthesis and decay rates of RNAs, which demonstrate how cells dynamically change the regulation of gene expression in response to both internal and external cues. Second, we discuss the underlying mechanisms of these changes in kinetics, including the functions of transcription factors and RNA-binding proteins. Overall, this review will help to clarify a system-level view of gene expression programs in cells.

Rapid and scalable profiling of nascent RNA with fastGRO

“…Steady-state RNA levels are the ultimate result of synthesis rate, RNA processing and RNA stability. Both RNA processing and stability are highly regulated in every cell type (Schoenberg and Maquat 2012; Pai and Luca 2019; Yamada and Akimitsu 2019). Therefore, RNA-seq alone is insufficient to infer the accurate transcriptional activity of any given gene.…”

Covalent labeling of nucleic acids

“…For thiol-reactive chemistry, which has proven particularly useful for studying transcriptional dynamics, we refer to recent review articles. 63,198 4.1.1 DNA labeling with alkyne-modified nucleosides. The most commonly used clickable label for DNA to date is the thymidine analog 5-ethynyl-2 0 -deoxyuridine (EdU) which is readily taken up by cells, metabolized to the corresponding triphosphate and efficiently incorporated into DNA (Fig.…”

A model explaining mRNA level fluctuations based on activity demands and RNA age

“…Detected cellular RNA levels are usually fluctuated (Deng et al, 2014;Briggs et al, 2018;Rodriguez et al, 2019). Studies have provided diverse explanations to the mechanisms of RNA level fluctuations (Elowitz and Leibler, 2000;Chubb et al, 2010;Baldazzi et al, 2012;Bar-Joseph et al, 2012;Stavreva et al, 2012;Briggs et al, 2018;Yamada and Akimitsu, 2019). However, limited transcriptomic techniques meant that some potential fundamental effects on RNA level fluctuations remained unknown.…”

“…Transcription and RNA degradation are key processes that lead to fluctuations in RNA levels (McManus et al, 2015;Yamada and Akimitsu, 2019). The detected cellular RNA levels within an experiment are not RNA amounts transcribed in the experimental period, but RNA abundance, which is RNA accumulation plus RNA transcription minus RNA degradation (Xu and Asakawa, 2019b).…”