Transcriptional Dynamics Reveal Critical Roles for Non-coding RNAs in the Immediate-Early Response

• DOI: 10.1371/journal.pcbi.1004217
• Publication Date: 2015-04-17T20:34:06Z
• Authors: Stuart Aitken; Shigeyuki Magi; Ahmad M. N. Alhendi; Masayoshi Itoh; Hideya Kawaji; Timo Lassmann; Carsten O. Daub; Erik Arner; Piero Carninci; Alistair R. R. Fo...; Yoshihide Hayashi...; ; Levon M. Khachigian; Mariko Okada-Hata...; Colin A. Semple
• Keywords: 0301 basic medicine; 570; RNA, Untranslated; Transcription, Genetic; Evolution; QH301-705.5; 2804 Cellular and Molecular Neuroscience; 612; 1105 Ecology; Immediate-Early Proteins; Cellular and Molecular Neuroscience; 03 medical and health sciences; Behavior and Systematics; 1311 Genetics; Modelling and Simulation; Genetics; 1312 Molecular Biology; Humans; Biology (General); Molecular Biology; Models, Statistical; Ecology; 000; Computational Biology; 2611 Modelling and Simulation; Kinetics; MicroRNAs; Computational Theory and Mathematics; MCF-7 Cells; 2303 Ecology; 1703 Computational Theory and Mathematics; Research Article

The immediate-early response mediates cell fate in to a variety of extracellular stimuli and is dysregulated many cancers. However, the specificity across types, roles non-coding RNAs are not well understood. Using large collection densely-sampled time series expression data we have examined induction unparalleled detail, types stimuli. We exploit cap analysis gene (CAGE) datasets directly measure promoter activities over time. novel method for identify transcripts with patterns that closely resemble dynamics known genes (IEGs) this enables comprehensive comparative study these their chromatin state. Surprisingly, suggest earliest transcriptional responses often involve promoters generating RNAs, which produced advance canonical protein-coding IEGs. IEGs be capable without de novo protein synthesis. Consistent this, find both RNA can explained by transcriptionally poised, permissive state prior stimulation. also explore function attenuation immediate early small sequencing dataset matched CAGE data: set microRNAs responsible IEG an estrogen receptor positive cancer line. Our computational statistical suited meta-analyses as there no requirement pass thresholds significant differential between points, it agnostic number points per dataset.