High-resolution sequencing and modeling identifies distinct dynamic RNA regulatory strategies

Michal Rabani, Raktima Raychowdhury, Marko Jovanovic, Michael Rooney, Deborah J. Stumpo, Andrea Pauli, Nir Hacohen, Alexander F. Schier, Perry J. Blackshear, Nir Friedman, Ido Amit, Aviv Regev*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

148 Scopus citations


Cells control dynamic transitions in transcript levels by regulating transcription, processing, and/or degradation through an integrated regulatory strategy. Here, we combine RNA metabolic labeling, rRNA-depleted RNA-seq, and DRiLL, a novel computational framework, to quantify the level; editing sites; and transcription, processing, and degradation rates of each transcript at a splice junction resolution during the LPS response of mouse dendritic cells. Four key regulatory strategies, dominated by RNA transcription changes, generate most temporal gene expression patterns. Noncanonical strategies that also employ dynamic posttranscriptional regulation control only a minority of genes, but provide unique signal processing features. We validate Tristetraprolin (TTP) as a major regulator of RNA degradation in one noncanonical strategy. Applying DRiLL to the regulation of noncoding RNAs and to zebrafish embryogenesis demonstrates its broad utility. Our study provides a new quantitative approach to discover transcriptional and posttranscriptional events that control dynamic changes in transcript levels using RNA sequencing data.

Original languageAmerican English
Pages (from-to)1698-1710
Number of pages13
Issue number7
StatePublished - 18 Dec 2014

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© 2014 Elsevier Inc. All rights reserved.


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