Title: Simultaneous Measurement of RNA Synthesis and Degradation Rates in Single Cells Unveils the Regulatory Mechanisms of Temporal RNA Dynamics

Authors: Siying Wang, Kun Yin, Jia Song, Shichao Lin*, Chaoyong Yang*

Abstract: The temporal dynamics of coordinated RNA transcription and degradation are heterogeneous among different cell types or states. However, current transcriptomic approaches are unable to simultaneously measure transcriptome-wide RNA synthesis and degradation rates in single cells for resolving the RNA regulatory mechanisms during dynamic processes. Herein, we develop scDUAL-seq, which integrates double nucleoside analogs pulse-pulse labeling, chemical nucleoside conversion, and single-cell RNA sequencing to record both RNA transcription and RNA degradation in heterogeneous cell populations. Compared to single nucleoside analog labeling-based methods, scDUAL-seq allows simultaneous recording of RNA transcription and degradation, leading to more accurate determination of RNA kinetic rates and RNA regulatory strategies. In a cortisol response model, scDUAL-seq enables the discovery of key regulons driving strategy transitions and elucidation of the coordinated regulation of RNA synthesis and degradation rates that control distinct strategy transitions. scDUAL-seq is expected to provide new insights into RNA regulatory mechanisms across diverse biological processes.

Full-Link: https://onlinelibrary.wiley.com/doi/10.1002/anie.202510939