TY  - JOUR
A1  - Bauer, Rebekka
A1  - Meyer, Sofie Patrizia
A1  - Kloss, Karolina Anna
A1  - Guerrero Ruiz, Vanesa Maria
A1  - Reuscher, Samira
A1  - Zhou, You
A1  - Fuhrmann, Dominik Christian
A1  - Zarnack, Katharina
A1  - Schmid, Tobias
A1  - Brüne, Bernhard
T1  - Functional RNA dynamics are progressively governed by RNA destabilization during the adaptation to chronic hypoxia
T2  - International journal of molecular sciences
N2  - 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.
KW  - hypoxia
KW  - monocytes
KW  - de novo transcription
KW  - RNA stability
KW  - SLAM-seq
KW  - GRAND-SLAM
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/83149
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-831493
SN  - 1422-0067
N1  - This work was supported by the DFG (BR999/25-1 to B.B.; SFB 1039, B04 to B.B.; GRK 2336, TP06 to B.B. and T.S.; SCHM2663/7-1 to T.S.; TRR 267, A1 to K.Z.). APC were funded by the Open Access Publication Fund of Goethe-University.
N1  - The sequencing data presented in this study are available in GEO accession number GSE199947.
VL  - 23
IS  - 10, art. 5824
SP  - 1
EP  - 19
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -