Functional RNA Dynamics Are Progressively Governed by RNA Destabilization during the Adaptation to Chronic Hypoxia
Previous studies towards reduced oxygen availability have mostly focused on changes in total mRNA expression, neglecting underlying transcriptional and post-transcriptional events. Therefore, we generated a comprehensive overview of hypoxia-induced changes in total mRNA expression, global de novo tr...
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/10/5824 |
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| author | Rebekka Bauer Sofie Patrizia Meyer Karolina Anna Kloss Vanesa Maria Guerrero Ruiz Samira Reuscher You Zhou Dominik Christian Fuhrmann Kathi Zarnack Tobias Schmid Bernhard Brüne |
| author_facet | Rebekka Bauer Sofie Patrizia Meyer Karolina Anna Kloss Vanesa Maria Guerrero Ruiz Samira Reuscher You Zhou Dominik Christian Fuhrmann Kathi Zarnack Tobias Schmid Bernhard Brüne |
| author_sort | Rebekka Bauer |
| collection | DOAJ |
| description | Previous studies towards reduced oxygen availability have mostly focused on changes in total mRNA expression, neglecting underlying transcriptional and post-transcriptional events. Therefore, we generated a comprehensive overview of hypoxia-induced changes in total mRNA expression, global de novo transcription, and mRNA stability in monocytic THP-1 cells. Since hypoxic episodes often persist for prolonged periods, we further compared the adaptation to acute and chronic hypoxia. While total mRNA changes correlated well with enhanced transcription during short-term hypoxia, mRNA destabilization gained importance under chronic conditions. Reduced mRNA stability not only added to a compensatory attenuation of immune responses, but also, most notably, to the reduction in nuclear-encoded mRNAs associated with various mitochondrial functions. These changes may prevent the futile production of new mitochondria under conditions where mitochondria cannot exert their full metabolic function and are indeed actively removed by mitophagy. The post-transcriptional mode of regulation might further allow for the rapid recovery of mitochondrial capacities upon reoxygenation. Our results provide a comprehensive resource of functional mRNA expression dynamics and underlying transcriptional and post-transcriptional regulatory principles during the adaptation to hypoxia. Furthermore, we uncover that RNA stability regulation controls mitochondrial functions in the context of hypoxia. |
| first_indexed | 2024-03-10T03:42:32Z |
| format | Article |
| id | doaj.art-74454da5c61341fd9d083ee61bfee189 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:42:32Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-74454da5c61341fd9d083ee61bfee1892023-11-23T11:29:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310582410.3390/ijms23105824Functional RNA Dynamics Are Progressively Governed by RNA Destabilization during the Adaptation to Chronic HypoxiaRebekka Bauer0Sofie Patrizia Meyer1Karolina Anna Kloss2Vanesa Maria Guerrero Ruiz3Samira Reuscher4You Zhou5Dominik Christian Fuhrmann6Kathi Zarnack7Tobias Schmid8Bernhard Brüne9Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, 60590 Frankfurt, GermanyFaculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, 60590 Frankfurt, GermanyFaculty of Biological Sciences, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-University Frankfurt, 60438 Frankfurt, GermanyFaculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, 60590 Frankfurt, GermanyFaculty of Biological Sciences, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-University Frankfurt, 60438 Frankfurt, GermanyFaculty of Biological Sciences, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-University Frankfurt, 60438 Frankfurt, GermanyFaculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, 60590 Frankfurt, GermanyFaculty of Biological Sciences, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe-University Frankfurt, 60438 Frankfurt, GermanyFaculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, 60590 Frankfurt, GermanyFaculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, 60590 Frankfurt, GermanyPrevious studies towards reduced oxygen availability have mostly focused on changes in total mRNA expression, neglecting underlying transcriptional and post-transcriptional events. Therefore, we generated a comprehensive overview of hypoxia-induced changes in total mRNA expression, global de novo transcription, and mRNA stability in monocytic THP-1 cells. Since hypoxic episodes often persist for prolonged periods, we further compared the adaptation to acute and chronic hypoxia. While total mRNA changes correlated well with enhanced transcription during short-term hypoxia, mRNA destabilization gained importance under chronic conditions. Reduced mRNA stability not only added to a compensatory attenuation of immune responses, but also, most notably, to the reduction in nuclear-encoded mRNAs associated with various mitochondrial functions. These changes may prevent the futile production of new mitochondria under conditions where mitochondria cannot exert their full metabolic function and are indeed actively removed by mitophagy. The post-transcriptional mode of regulation might further allow for the rapid recovery of mitochondrial capacities upon reoxygenation. Our results provide a comprehensive resource of functional mRNA expression dynamics and underlying transcriptional and post-transcriptional regulatory principles during the adaptation to hypoxia. Furthermore, we uncover that RNA stability regulation controls mitochondrial functions in the context of hypoxia.https://www.mdpi.com/1422-0067/23/10/5824hypoxiamonocytesde novo transcriptionRNA stabilitySLAM-seqGRAND-SLAM |
| spellingShingle | Rebekka Bauer Sofie Patrizia Meyer Karolina Anna Kloss Vanesa Maria Guerrero Ruiz Samira Reuscher You Zhou Dominik Christian Fuhrmann Kathi Zarnack Tobias Schmid Bernhard Brüne Functional RNA Dynamics Are Progressively Governed by RNA Destabilization during the Adaptation to Chronic Hypoxia International Journal of Molecular Sciences hypoxia monocytes de novo transcription RNA stability SLAM-seq GRAND-SLAM |
| title | Functional RNA Dynamics Are Progressively Governed by RNA Destabilization during the Adaptation to Chronic Hypoxia |
| title_full | Functional RNA Dynamics Are Progressively Governed by RNA Destabilization during the Adaptation to Chronic Hypoxia |
| title_fullStr | Functional RNA Dynamics Are Progressively Governed by RNA Destabilization during the Adaptation to Chronic Hypoxia |
| title_full_unstemmed | Functional RNA Dynamics Are Progressively Governed by RNA Destabilization during the Adaptation to Chronic Hypoxia |
| title_short | Functional RNA Dynamics Are Progressively Governed by RNA Destabilization during the Adaptation to Chronic Hypoxia |
| title_sort | functional rna dynamics are progressively governed by rna destabilization during the adaptation to chronic hypoxia |
| topic | hypoxia monocytes de novo transcription RNA stability SLAM-seq GRAND-SLAM |
| url | https://www.mdpi.com/1422-0067/23/10/5824 |
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