Chromatin measurements reveal contributions of synthesis and decay to steady‐state mRNA levels
Abstract Messenger RNA levels in eukaryotes are controlled by multiple consecutive regulatory processes, which can be classified into two layers: primary transcriptional regulation at the chromosomal level and secondary, co‐ and post‐transcriptional regulation of the mRNA. To identify the individual...
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| Format: | Article |
| Language: | English |
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Springer Nature
2012-07-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2012.23 |
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| _version_ | 1849235642285817856 |
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| author | Sylvia C Tippmann Robert Ivanek Dimos Gaidatzis Anne Schöler Leslie Hoerner Erik van Nimwegen Peter F Stadler Michael B Stadler Dirk Schübeler |
| author_facet | Sylvia C Tippmann Robert Ivanek Dimos Gaidatzis Anne Schöler Leslie Hoerner Erik van Nimwegen Peter F Stadler Michael B Stadler Dirk Schübeler |
| author_sort | Sylvia C Tippmann |
| collection | DOAJ |
| description | Abstract Messenger RNA levels in eukaryotes are controlled by multiple consecutive regulatory processes, which can be classified into two layers: primary transcriptional regulation at the chromosomal level and secondary, co‐ and post‐transcriptional regulation of the mRNA. To identify the individual contribution of these layers to steady‐state RNA levels requires separate quantification. Using mouse as a model organism, we show that chromatin features are sufficient to model RNA levels but with different sensitivities in dividing versus postmitotic cells. In both cases, chromatin‐derived transcription rates explain over 80% of the observed variance in measured RNA levels. Further inclusion of measurements of mRNA half‐life and microRNA expression data enabled the identification of a low quantitative contribution of RNA decay by either microRNA or general differential turnover to final mRNA levels. Together, this establishes a chromatin‐based quantitative model for the contribution of transcriptional and post‐transcriptional processes to steady‐state levels of messenger RNA. |
| format | Article |
| id | doaj-art-c3e6bbbe1fdc410388088022b5a6ecb4 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2012-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-c3e6bbbe1fdc410388088022b5a6ecb42025-08-20T04:02:44ZengSpringer NatureMolecular Systems Biology1744-42922012-07-018111110.1038/msb.2012.23Chromatin measurements reveal contributions of synthesis and decay to steady‐state mRNA levelsSylvia C Tippmann0Robert Ivanek1Dimos Gaidatzis2Anne Schöler3Leslie Hoerner4Erik van Nimwegen5Peter F Stadler6Michael B Stadler7Dirk Schübeler8Friedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchBiozentrum, University of Basel, and Swiss Institute of BioinformaticsDepartment of Theoretical Chemistry, University of ViennaFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchAbstract Messenger RNA levels in eukaryotes are controlled by multiple consecutive regulatory processes, which can be classified into two layers: primary transcriptional regulation at the chromosomal level and secondary, co‐ and post‐transcriptional regulation of the mRNA. To identify the individual contribution of these layers to steady‐state RNA levels requires separate quantification. Using mouse as a model organism, we show that chromatin features are sufficient to model RNA levels but with different sensitivities in dividing versus postmitotic cells. In both cases, chromatin‐derived transcription rates explain over 80% of the observed variance in measured RNA levels. Further inclusion of measurements of mRNA half‐life and microRNA expression data enabled the identification of a low quantitative contribution of RNA decay by either microRNA or general differential turnover to final mRNA levels. Together, this establishes a chromatin‐based quantitative model for the contribution of transcriptional and post‐transcriptional processes to steady‐state levels of messenger RNA.https://doi.org/10.1038/msb.2012.23chromatinhistone modificationsmicroRNARNA decaytranscriptional regulation |
| spellingShingle | Sylvia C Tippmann Robert Ivanek Dimos Gaidatzis Anne Schöler Leslie Hoerner Erik van Nimwegen Peter F Stadler Michael B Stadler Dirk Schübeler Chromatin measurements reveal contributions of synthesis and decay to steady‐state mRNA levels Molecular Systems Biology chromatin histone modifications microRNA RNA decay transcriptional regulation |
| title | Chromatin measurements reveal contributions of synthesis and decay to steady‐state mRNA levels |
| title_full | Chromatin measurements reveal contributions of synthesis and decay to steady‐state mRNA levels |
| title_fullStr | Chromatin measurements reveal contributions of synthesis and decay to steady‐state mRNA levels |
| title_full_unstemmed | Chromatin measurements reveal contributions of synthesis and decay to steady‐state mRNA levels |
| title_short | Chromatin measurements reveal contributions of synthesis and decay to steady‐state mRNA levels |
| title_sort | chromatin measurements reveal contributions of synthesis and decay to steady state mrna levels |
| topic | chromatin histone modifications microRNA RNA decay transcriptional regulation |
| url | https://doi.org/10.1038/msb.2012.23 |
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