The role of RNA processing dynamics in the responsiveness of mature RNA. (A) Premature and mature RNA abundances and the value of the RNA kinetic rates for two genes with fast (k 2 =20) and slow (k 2 =0.2) processing dynamics. The corresponding profiles of increased abundance of premature and mature RNA following a doubling in the rate of synthesis (k 1 ) are indicated on the right. (B) Distributions of RNA kinetic rates in untreated 3T9 fibroblast cells. (C) Percentage of genes with reduced responsiveness following the indicated N-fold modulation of the kinetic rate(s). (D) RNA-seq samples are colour-coded according to the corresponding tissue-type and median values of í µí¼ and í µí»¥ for protein-coding RNAs are reported. (E-F) as in (D) for pseudogenes and long non-coding RNAs, respectively.

The role of RNA processing dynamics in the responsiveness of mature RNA. (A) Premature and mature RNA abundances and the value of the RNA kinetic rates for two genes with fast (k 2 =20) and slow (k 2 =0.2) processing dynamics. The corresponding profiles of increased abundance of premature and mature RNA following a doubling in the rate of synthesis (k 1 ) are indicated on the right. (B) Distributions of RNA kinetic rates in untreated 3T9 fibroblast cells. (C) Percentage of genes with reduced responsiveness following the indicated N-fold modulation of the kinetic rate(s). (D) RNA-seq samples are colour-coded according to the corresponding tissue-type and median values of í µí¼ and í µí»¥ for protein-coding RNAs are reported. (E-F) as in (D) for pseudogenes and long non-coding RNAs, respectively.

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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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... post-transcriptional regulation heatmaps revealed that changes in the k 2 /k 3 ratio automatically grouped together samples from similar types of tissues and diseases (Fig. 4B, Supplementary Fig. 4). This suggested that post-transcriptional regulation is coordinated across similar conditions, and revealed that some types of cells have a tendency to be markedly subjected to post-transcriptional regulation (Supplementary Fig. 5). Interestingly, ~30% of the information contained in the clustering derived from the post-transcriptional regulation category, and could not be obtained based on tissue-specific expression patterns (Supplementary Fig. 6). ...
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... species can provide information on the post-transcriptional dynamics (Fig. 4), and, more specifically, on the influence that processing rates can have on RNA responsiveness. Indeed, while RNA stability is currently considered to be the major determinant of responsiveness 3 , our analyses indicate that this can also be affected by RNA processing (Fig. ...
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... solutions, respectively; Supplementary Fig. 7). The responsiveness of genes scoring high in both metrics (í µí»¥>1 and í µí¼>1.5) is thus significantly dampened by the processing step. In physiological conditions (3T9 mouse fibroblast cells 14 ), processing rates were found to be extremely rapid in comparison to synthesis and degradation rates (Fig. 5B), and had to be significantly reduced for a substantial number of genes to become affected. For example, around 10% of genes were impacted by a 4-fold reduction in their processing rates (Fig. 5C). Nonetheless, the impact of a reduced processing rate was markedly dependent on the values of the other two kinetic rates. Indeed, halving ...
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... conditions (3T9 mouse fibroblast cells 14 ), processing rates were found to be extremely rapid in comparison to synthesis and degradation rates (Fig. 5B), and had to be significantly reduced for a substantial number of genes to become affected. For example, around 10% of genes were impacted by a 4-fold reduction in their processing rates (Fig. 5C). Nonetheless, the impact of a reduced processing rate was markedly dependent on the values of the other two kinetic rates. Indeed, halving processing rates impacted 10% of the genes, if combined with a two-fold increase of both synthesis and degradation rates (Fig. 5C). It is currently unclear whether physiological or pathological ...
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... 10% of genes were impacted by a 4-fold reduction in their processing rates (Fig. 5C). Nonetheless, the impact of a reduced processing rate was markedly dependent on the values of the other two kinetic rates. Indeed, halving processing rates impacted 10% of the genes, if combined with a two-fold increase of both synthesis and degradation rates (Fig. 5C). It is currently unclear whether physiological or pathological conditions exist where RNA maturation can be slowed down to the point of becoming an impediment to the fast response required in cases such as stress response. This prompted us to characterize this phenomenon in various cell types and disease conditions. Median í µí¼ and ...
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... response required in cases such as stress response. This prompted us to characterize this phenomenon in various cell types and disease conditions. Median í µí¼ and í µí»¥ were quantified for each sample in the dataset examined in Fig. 4. Tissue types whose samples had similar metrics were highlighted and colour coded for three classes of genes ( Fig. 5D-F). In comparison to protein-coding and pseudo genes, long non coding RNAs (lncRNAs) had higher metrics overall. For all three classes of genes, samples from smooth muscle, immune system, CD19+ B-cells, kidney and breast, consistently returned high values of í µí¼ and í µí»¥. In other words, these tissue types are expected to be ...

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