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Functional RNA dynamics are progressively governed by RNA destabilization during the adaptation to chronic hypoxia

ABSTRACT: Previous studies towards reduced oxygen availability 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 epi-sodes often persist for prolonged periods, we further compared adaptations 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 compensatory attenuation of immune responses, but most no-tably to the reduction of nuclear-encoded mRNAs associated with various mitochondrial func-tions. 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 rapid recov-ery of mitochondrial capacities upon reoxygenation. Our results provide a comprehensive re-source of functional mRNA expression dynamics and underlying transcriptional and post-transcriptional regulatory principles during the adaptation to hypoxia. Furthermore, we specifically uncover mitochondrial functions controlled by RNA stability regulation in the con-text of hypoxia.

ORGANISM(S): Homo sapiens

PROVIDER: GSE199947 | GEO | 2022/06/01

REPOSITORIES: GEO

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Functional RNA dynamics are progressively governed by RNA destabilization during the adaptation to chronic hypoxia

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