Genome-wide dynamics of RNA synthesis, processing, and degradation without RNA metabolic labeling
- Mattia Furlan1,2,
- Eugenia Galeota1,
- Nunzio Del Gaudio1,
- Erik Dassi3,
- Michele Caselle2,
- Stefano de Pretis1,4 and
- Mattia Pelizzola1,4
- 1Center for Genomic Science, Fondazione Istituto Italiano di Tecnologia, 20139 Milan, Italy;
- 2Physics Department and INFN, University of Turin, 10125 Turin, Italy;
- 3Centre for Integrative Biology, University of Trento, 38123 Trento, Italy
-
↵4 These authors contributed equally to this work.
Abstract
The quantification of the kinetic rates of RNA synthesis, processing, and degradation are largely based on the integrative analysis of total and nascent transcription, the latter being quantified through RNA metabolic labeling. We developed INSPEcT−, a computational method based on the mathematical modeling of premature and mature RNA expression that is able to quantify kinetic rates from steady-state or time course total RNA-seq data without requiring any information on nascent transcripts. Our approach outperforms available solutions, closely recapitulates the kinetic rates obtained through RNA metabolic labeling, improves the ability to detect changes in transcript half-lives, reduces the cost and complexity of the experiments, and can be adopted to study experimental conditions in which nascent transcription cannot be readily profiled. Finally, we applied INSPEcT− to the characterization of post-transcriptional regulation landscapes in dozens of physiological and disease conditions. This approach was included in the INSPEcT Bioconductor package, which can now unveil RNA dynamics from steady-state or time course data, with or without the profiling of nascent RNA.
Footnotes
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.260984.120.
-
Freely available online through the Genome Research Open Access option.
- Received January 10, 2020.
- Accepted August 21, 2020.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
