Characterization of time course RNA dynamics: reanalysis of four published datasets. (A) Percentage of genes that, following the activation of MYC and T cell differentiation, are subjected to the regulation of synthesis (transcriptional response), processing and/or degradation (post-transcriptional response) or both (mixed transcriptional and post-transcriptional response). (B) Fold change profiles of premature and total RNA abundance and the RNA kinetic rates for two key regulators of human T cell differentiation (RORC and SATB1) in Th17 and control Th0 cells. (C) Median Log2 fold changes for total RNA, synthesis and degradation rates in response to the expression of miR-124; miRNA targets and non-targeted genes are compared. (D) A. thaliana genes were divided in four groups based on the RNA kinetic rates; the distribution of each rate within each cluster is shown in the boxplots. (E) RNA dynamics of A. thaliana genes modulated in at least one kinetic rate following ethylene treatment; changes in premature and total RNA abundance and the kinetic rates compared to the untreated condition are shown.

Characterization of time course RNA dynamics: reanalysis of four published datasets. (A) Percentage of genes that, following the activation of MYC and T cell differentiation, are subjected to the regulation of synthesis (transcriptional response), processing and/or degradation (post-transcriptional response) or both (mixed transcriptional and post-transcriptional response). (B) Fold change profiles of premature and total RNA abundance and the RNA kinetic rates for two key regulators of human T cell differentiation (RORC and SATB1) in Th17 and control Th0 cells. (C) Median Log2 fold changes for total RNA, synthesis and degradation rates in response to the expression of miR-124; miRNA targets and non-targeted genes are compared. (D) A. thaliana genes were divided in four groups based on the RNA kinetic rates; the distribution of each rate within each cluster is shown in the boxplots. (E) RNA dynamics of A. thaliana genes modulated in at least one kinetic rate following ethylene treatment; changes in premature and total RNA abundance and the kinetic rates compared to the untreated condition are shown.

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The kinetic rates of RNA synthesis, processing and degradation determine the dynamics of transcriptional regulation by governing both the abundance and the responsiveness to modulations of premature and mature RNA species. The study of RNA dynamics is largely based on the integrative analysis of total and nascent transcription, with the latter bein...

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... a change in RNA synthesis was observed for 95% of the MYC modulated genes, while an alteration of either processing or degradation rates was seen in 41% of cases (Fig. 3A, Supplementary . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in ...
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... bioRxiv preprint first posted online Jan. 14, 2019; Fig. 2). Importantly, this dataset also revealed a high correlation between estimated kinetic rates and those derived from the integrative analysis of total and nascent RNA-seq data (0.91, 0.48 and 0.69 Spearman correlation for synthesis, processing and degradation rates, respectively, Supplementary Fig. 3). Secondly, we reanalysed the temporal polarization of CD4+ cells with (Th17) or without (Th0) polarizing cytokines 20 . ...
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... in comparison with the response elicited by a master transcription factor of the likes of MYC, more genes were modulated through post-transcriptional regulation (67% of genes, Fig. 3A, Supplementary Fig. 2). Key regulators of this process were permanently or temporarily modulated in Th17 cells, while changing only transiently in Th0 control cells (Fig. 3B). Our analyses revealed underlying mechanisms of regulation that rely on the control of RNA synthesis in the case of the RORC master regulator and of post-transcriptional regulation in that of SATB1 (Fig. 3B). Next, we analysed the time-course response to the activation of two microRNAs 21 . We expected to see a strong ...
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... Key regulators of this process were permanently or temporarily modulated in Th17 cells, while changing only transiently in Th0 control cells (Fig. 3B). Our analyses revealed underlying mechanisms of regulation that rely on the control of RNA synthesis in the case of the RORC master regulator and of post-transcriptional regulation in that of SATB1 (Fig. 3B). Next, we analysed the time-course response to the activation of two microRNAs 21 . We expected to see a strong post-transcriptional regulation of the miRNA target transcripts and, indeed, these were seen to be primarily controlled at the level of their stability, while non-target transcripts remained mostly unaffected (Fig. 3C). ...
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... in that of SATB1 (Fig. 3B). Next, we analysed the time-course response to the activation of two microRNAs 21 . We expected to see a strong post-transcriptional regulation of the miRNA target transcripts and, indeed, these were seen to be primarily controlled at the level of their stability, while non-target transcripts remained mostly unaffected (Fig. 3C). Finally, we provided the first analysis of RNA dynamics in plants by focusing on the temporal response to ethylene in Arabidopsis thaliana 22 ...
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... modelled RNA dynamics for 564 genes, 81 of which were found to be modulated at the level of total or premature RNA (Fig. 3E). Responsive genes were divided into four clusters according to their RNA kinetic rates in the untreated condition. The first cluster included genes involved in cellular respiration, with high rates of both synthesis and degradation, denoted by high responsiveness (Fig. 3D). 70 genes were found to be regulated only through changes in ...
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... of which were found to be modulated at the level of total or premature RNA (Fig. 3E). Responsive genes were divided into four clusters according to their RNA kinetic rates in the untreated condition. The first cluster included genes involved in cellular respiration, with high rates of both synthesis and degradation, denoted by high responsiveness (Fig. 3D). 70 genes were found to be regulated only through changes in RNA synthesis, while 11 genes were exclusively regulated post-transcriptionally (Fig. 3E). Notably, the latter included AT1G79700 (WRI4), a newly identified factor of the ethylene signalling pathway, which we revealed to be specifically regulated through an increase in its ...
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... RNA kinetic rates in the untreated condition. The first cluster included genes involved in cellular respiration, with high rates of both synthesis and degradation, denoted by high responsiveness (Fig. 3D). 70 genes were found to be regulated only through changes in RNA synthesis, while 11 genes were exclusively regulated post-transcriptionally (Fig. 3E). Notably, the latter included AT1G79700 (WRI4), a newly identified factor of the ethylene signalling pathway, which we revealed to be specifically regulated through an increase in its RNA stability (Fig. ...
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... 70 genes were found to be regulated only through changes in RNA synthesis, while 11 genes were exclusively regulated post-transcriptionally (Fig. 3E). Notably, the latter included AT1G79700 (WRI4), a newly identified factor of the ethylene signalling pathway, which we revealed to be specifically regulated through an increase in its RNA stability (Fig. ...

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... This model is implemented, with various assumptions, by different tools [cDTA (Sun et al., 2012), DRiLL (Rabani et al., 2014), INSPEcT (de Pretis et al., 2015) and pulseR (Uvarovskii and Dieterich, 2017)], which rely on the quantification of both nascent and total RNA species, the former profiled through RNA metabolic labeling (Dolken et al., 2008). Recently, novel approaches are being developed that do not require the quantification of nascent RNA, to estimate the full set (Furlan et al., 2019), or a subset of the kinetic rates (Zeisel et al., 2011;Gray et al., 2014;La Manno et al., 2018). Despite the availability of these tools, anticipating the outcome of the joint contribution of various RNA life-cycle stages can be far from trivial. ...
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