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Mitochondria drive neuronal differentiation by metabolising nuclear-encoded RNA

ABSTRACT: Mitochondria drive neuronal differentiation by metabolising nuclear-encoded RNA

PROVIDER: PRJNA954742 | ENA |

REPOSITORIES: ENA

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Mitochondria drive neuronal differentiation by metabolising nuclear-encoded RNA [ATAC-seq]

Project description:Mitochondria drive neuronal differentiation by metabolising nuclear-encoded RNA [ATAC-seq]

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Project description:Mitochondria drive neuronal differentiation by metabolising nuclear-encoded RNA [RNA-seq]

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Mitochondria drive neuronal differentiation by metabolising nuclear-encoded RNA [RNA-seq]

Project description:In this study, we show that within minutes of exposure to differentiation cues and activation of the electron transport chain, the mitochondrial outer membrane transiently fuses with the nuclear membrane of neural progenitors, leading to efflux of the nuclear-encoded RNAs (neRNA) into the positively charged mitochondrial intermembrane space. Subsequent degradation of mitochondrial neRNAs by Polynucleotide phosphorylase 1 (Pnpt1) residing in the intermembrane space curbs the transcriptomic memory of progenitor cells. Further, phosphorolysis by Pnpt1 indirectly suppresses ATP production by depriving ATP synthase of inorganic phosphate, resulting in delayed recovery of the attenuated transcriptomic memory. Collectively, these events force the progenitor cells towards a “tipping point” characterised by emergence of a competing neuronal differentiation program.

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Mitochondria drive neuronal differentiation by metabolising nuclear-encoded RNA [ATAC-seq]

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Mitochondria drive neuronal differentiation by metabolising nuclear-encoded RNA

Project description:This SuperSeries is composed of the SubSeries listed below.

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Purification of mitochondria from skeletal muscle tissue for transcriptomic analyses reveals localization of nuclear-encoded non-coding RNAs [SMvsMT]

Project description:Mitochondria are central to cellular function, particularly in metabolically active tissues such as skeletal muscle. Nuclear-encoded RNAs typically localise within the nucleus and cytosol but a small population may also translocate to subcellular compartments such as mitochondria. We aimed to investigate the nuclear-encoded RNAs that localise within the mitochondria of skeletal muscle tissue. Intact mitochondria were isolated via immunoprecipitation (IP) followed by enzymatic treatments (RNase-A and proteinase-K) optimised to remove transcripts located exterior to mitochondria, making it amenable for high-throughput transcriptomic sequencing. Whole-transcriptome RNA sequencing of enzymatically-purified mitochondria isolated by IP from skeletal muscle tissue showed a high degree of purity. In summary, we describe a novel, powerful sequencing approach applicable to animal and human tissues and cells that can facilitate the discovery of nuclear-encoded RNA transcripts localised within skeletal muscle mitochondria.

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Purification of mitochondria from skeletal muscle tissue for transcriptomic analyses reveals localization of nuclear-encoded non-coding RNAs [Mitoplasts]

Project description:Mitochondria are central to cellular function, particularly in metabolically active tissues such as skeletal muscle. Nuclear-encoded RNAs typically localise within the nucleus and cytosol but a small population may also translocate to subcellular compartments such as mitochondria. We aimed to investigate the nuclear-encoded RNAs that localise within the mitochondria of skeletal muscle cells and tissue. Intact mitochondria were isolated via immunoprecipitation (IP) followed by enzymatic treatments (RNase-A and proteinase-K) to remove transcripts located exterior to mitochondria, making it amenable for high-throughput transcriptomic sequencing. Whole-transcriptome RNA sequencing of enzymatically-purified mitochondria isolated by IP from skeletal muscle tissue showed a striking similarity in the degree of purity compared to mitoplast preparations which lack an outer mitochondrial membrane. In summary, we describe a novel, powerful sequencing approach applicable to animal and human tissues and cells that can facilitate the discovery of nuclear-encoded RNA transcripts localised within skeletal muscle mitochondria.

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