Understanding spatiotemporal coupling of gene expression using single molecule RNA imaging technologies

Across all kingdoms of life, gene regulatory mechanisms underlie cellular adaptation to ever-changing environments. Regulation of gene expression adjusts protein synthesis and, in turn, cellular growth. Messenger RNAs are key molecules in the process of gene expression. Our ability to quantitatively measure mRNA expression in single cells has improved tremendously over the past decades. This revealed an unexpected coordination between the steps that control the life of an mRNA, from transcription to degradation. Here, we provide an overview of the state-of-the-art imaging approaches for measurement and quantitative understanding of gene expression, starting from the early visualizations of single genes by electron microscopy to current fluorescence-based approaches in single cells, including live-cell RNA-imaging approaches to FISH-based spatial transcriptomics across model organisms. We also highlight how these methods have shaped our current understanding of the spatiotemporal coupling between transcriptional and post-transcriptional events in prokaryotes. We conclude by discussing future challenges of this multidisciplinary field.

Automated summary

Gene regulatory mechanisms play a crucial role in cellular adaptation to changing environments. mRNA is a key molecule in gene expression and its quantitative measurement in single cells has greatly improved over the past decades. This article provides an overview of state-of-the-art imaging approaches for measuring and understanding gene expression, highlighting the coordination between transcription and degradation of mRNA. The article also discusses future challenges in this multidisciplinary field.