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Published on: August 10, 2021
A conserved mammalian mecciRNA, mecciATP6, regulates mitochondrial homeostasis through interaction with HNRNPA3
Xiaoyang Cao1, Juzheng Sui1, Ge Shan1
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, 230027, China.
Abstract:
Circular RNAs (circRNAs) are covalently closed, single-stranded RNA molecules generated from both nuclear and mitochondrial genomes. Several nuclear-encoded circRNAs have been reported to be conserved in sequence and function across animals. However, the evolutionary conservation and physiological significance of mitochondria-encoded circRNAs (mecciRNAs) remain largely unexplored. Here, by analyzing mitochondrial RNA sequencing data from human and mouse cells, we identify a conserved mecciRNA derived from the MT-ATP6 locus, termed mecciATP6. We show that mecciATP6 modulates mitochondrial homeostasis by binding and regulating the protein abundance of an evolutionarily conserved RNA-binding protein (RBP) HNRNPA3. Our data provide a conceptual framework for defining mecciRNA conservation across mammals and uncover a conserved mecciRNA-protein regulatory mechanism linked to mitochondrial homeostasis.
Insights
Mitochondria-encoded circular RNAs (mecciRNAs) are newly explored for their conservation. Researchers identified a conserved mecciRNA, mecciATP6, that regulates mitochondrial homeostasis by interacting with HNRNPA3.
Area of Science:
- Mitochondrial biology
- RNA biology
- Genomics
Background:
- Circular RNAs (circRNAs) are RNA molecules with a covalent loop structure.
- Nuclear-encoded circRNAs are conserved across species, but mitochondria-encoded circRNAs (mecciRNAs) are understudied.
- The evolutionary conservation and function of mecciRNAs are largely unknown.
Purpose of the Study:
- To investigate the evolutionary conservation of mecciRNAs.
- To explore the physiological significance of mecciRNAs.
- To identify conserved mecciRNA-protein interactions in mammals.
Main Methods:
- Analysis of mitochondrial RNA sequencing data from human and mouse cells.
- Identification and characterization of a novel mecciRNA.
- Investigation of mecciRNA-protein interactions using molecular biology techniques.
Main Results:
- A conserved mecciRNA, mecciATP6, derived from the MT-ATP6 gene locus was identified in human and mouse cells.
- mecciATP6 was shown to regulate mitochondrial homeostasis.
- mecciATP6 binds to and regulates the protein abundance of the RNA-binding protein HNRNPA3.
Conclusions:
- This study establishes a framework for defining mecciRNA conservation across mammals.
- A conserved regulatory mechanism involving a mecciRNA and an RNA-binding protein (HNRNPA3) linked to mitochondrial homeostasis was uncovered.
- The findings highlight the functional importance of mecciRNAs in cellular physiology.
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