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Developmental conservation of microRNA gene localization at the nuclear periphery.

ABSTRACT: microRNAs are of vital importance for the regulation of the adaptive and innate immune responses, modulating gene expression at the post transcriptional level. Although there is cumulative information regarding the steady state mature microRNA levels and their respective targets, little is known about the effect of the three-dimensional chromatin architecture on the transcriptional regulation of microRNA gene loci. Here, we sought to investigate the effect of subnuclear localization on the transcriptional activation of eight murine microRNA loci in the immune system. Our results show that microRNA genes display a preferential monoallelic gene expression profile accompanied with perinuclear localization irrespectively of their transcription status or differentiation state. The expression profile and perinuclear localization are developmentally conserved while microRNA gene loci localization outside constitutive lamin associated domains is cross-species conserved. Our findings provide support for an active nuclear periphery and its role in chromatin organization of the non-coding genome.

SUBMITTER: Salataj E

PROVIDER: S-EPMC6827902 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Developmental conservation of microRNA gene localization at the nuclear periphery.

Salataj Eralda E Stathopoulou Chrysoula C Hafþórsson Róbert A RA Nikolaou Christoforos C Spilianakis Charalampos G CG

PloS one 20191104 11

microRNAs are of vital importance for the regulation of the adaptive and innate immune responses, modulating gene expression at the post transcriptional level. Although there is cumulative information regarding the steady state mature microRNA levels and their respective targets, little is known about the effect of the three-dimensional chromatin architecture on the transcriptional regulation of microRNA gene loci. Here, we sought to investigate the effect of subnuclear localization on the trans ...[more]

PMID: 31682635

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Project description:ORF73 latency-associated nuclear antigen (LANA) of the Kaposi's sarcoma-associated herpesvirus (KSHV) is targeted to the nucleus of infected cells where it binds to chromatin and mediates viral episome persistence, interacts with cellular proteins and plays a role in latency and tumorigenesis. A structurally related LANA homolog has been identified in the retroperitoneal fibromatosis herpesvirus (RFHV), the macaque homolog of KSHV. Here, we report the evolutionary and functional conservation of a novel bi-functional nuclear localization signal (NLS) in KSHV and RFHV LANA. N-terminal peptides from both proteins were fused to EGFP or double EGFP fusions to examine their ability to induce nuclear transport of a heterologous protein. In addition, GST-pull down experiments were used to analyze the ability of LANA peptides to interact with members of the karyopherin family of nuclear transport receptors. Our studies revealed that both LANA proteins contain an N-terminal arginine/glycine (RG)-rich domain spanning a conserved chromatin-binding motif, which binds directly to importin ?1 in a RanGTP-sensitive manner and serves as an NLS in the importin ?1-mediated non-classical nuclear import pathway. Embedded within this domain is a conserved lysine/arginine-(KR)-rich bipartite motif that binds directly to multiple members of the importin ? family of nuclear import adaptors in a RanGTP-insensitive manner and serves as an NLS in the classical importin ?/?-mediated nuclear import pathway. The positioning of a classical bipartite kr-NLS embedded within a non-classical rg-NLS is a unique arrangement in these viral proteins, whose nuclear localization is critical to their functionality and to the virus life cycle. The ability to interact with multiple import receptors provides alternate pathways for nuclear localization of LANA. Since different import receptors can import cargo to distinct subnuclear compartments, a multifunctional NLS may provide LANA with an increased ability to interact with different nuclear components in its multifunctional role to maintain viral latency.

Dataset Information

Developmental conservation of microRNA gene localization at the nuclear periphery.

Publications

Developmental conservation of microRNA gene localization at the nuclear periphery.

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