Distinct transcription kinetics of pluripotent cell states. Issue 1 (12th January 2022)

• Record Type: Journal Article
• Authors: Shao, Rui; Kumar, Banushree; Lidschreiber, Katja; Lidschreiber, Michael; Cramer, Patrick; Elsässer, Simon J
• Is Part Of: Molecular systems biology. Volume 18:Issue 1(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-12
• Subjects: mouse pluripotent stem cells -- transcription termination -- transcription unit annotation -- transcription velocity -- transient transcriptome sequencing; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.15252/msb.202110407
• Languages: English
• ISSNs: 1744-4292

Abstract

Abstract: Mouse embryonic stem cells (mESCs) can adopt naïve, ground, and paused pluripotent states that give rise to unique transcriptomes. Here, we use transient transcriptome sequencing (TT‐seq) to define both coding and non‐coding transcription units (TUs) in these three pluripotent states and combine TT‐seq with RNA polymerase II occupancy profiling to unravel the kinetics of RNA metabolism genome‐wide. Compared to the naïve state (serum), RNA synthesis and turnover rates are globally reduced in the ground state (2i) and the paused state (mTORi). The global reduction in RNA synthesis goes along with a genome‐wide decrease of polymerase elongation velocity, which is related to epigenomic features and alterations in the Pol II termination window. Our data suggest that transcription activity is the main determinant of steady state mRNA levels in the naïve state and that genome‐wide changes in transcription kinetics invoke ground and paused pluripotent states. SYNOPSIS: Genome‐wide analyses of RNA metabolism kinetics in naïve, ground and paused pluripotent mouse embryonic stem cells (mESCs) indicate that the three states show markedly different global transcriptional kinetics. Transient transcriptome sequencing (TT‐seq) is used to annotate transcription units in mESC pluripotent states. Transcription reduction in the early state transitions is liked to lower total RNA abundance and turnover rates. Genome‐wide changes in transcription kinetics invoke ground and paused pluripotent states. The estimated elongation velocity connects with RNA Pol II pause‐release and termination distance. Abstract : Genome‐wide analyses of RNA metabolism kinetics in naïve, ground and paused pluripotent mouse embryonic stem cells (mESCs) indicate that the three states show markedly different global transcriptional kinetics.