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Life-long persistence of nuclear RNAs in the mouse brain

ABSTRACT: Life-long persistence of nuclear RNAs in the mouse brain

PROVIDER: PRJNA1041766 | ENA |

REPOSITORIES: ENA

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Life-long persistence of nuclear RNAs in the mouse brain [Hippocampus]

Project description:Genomic DNA residing in the nuclei of mammalian neurons can be as old as the organism itself. The life span of non-coding nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. Here, we report the identification and characterization of nuclear RNAs that do not turn over for at least two years in the adult mouse brain. These long-lived RNAs (LL-RNA) are stably retained in nuclei in a neural cell type-specific manner and are required for the maintenance of heterochromatin. Thus, the remarkable life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information but also the extreme stability of RNA for the functional organization of chromatin.

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Life-long persistence of nuclear RNAs in the mouse brain

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

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Long read sequencing of nuclear RNAs from human coronary artery smooth muscle cells

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Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx

Project description:Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx

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Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx

Project description:In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication and acts as host gene trans-regulator. However, functionally relevant spatiotemporal localization and interactions of cccDNA and HBx remain to be understood. This is the first study utilizing circularized chromosome conformation capture (4C) to identify regional virus-host genome interactions. We combined 4C with RNA-seq and ChIP-seq to illuminate the nuclear landscape associated with HBV episomes and HBx. Moreover, we functionally studied HBx-binding to episomal HBV DNA. In human HBV-positive HepaRG hepatocytes, 4C and ChIP revealed specific nuclear localization of HBV episomes and HBx associated with actively transcribed nuclear domains correlating well in size with constrained topological units built up by chromatin fibre loops, which are believed to constitute fundamental cell nuclear architectural units. Interestingly, HBx alone occupied transcribed chromatin domains, and its binding to HBV episomes depended on its C-terminus in vitro. In conclusion, HBx and HBV DNA similarly follow higher-order nuclear assembly patterns, specifically favoring transcriptionally active nuclear compartments. These novel observations may shed light on important unsolved problems: to understand the long-term episomal stability and the facilitation of viral persistence.

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