Dataset Information

Intragenic MicroRNAs Autoregulate Their Host Genes in Both Direct and Indirect Ways-A Cross-Species Analysis.

ABSTRACT: MicroRNAs (miRNAs) function as master switches for post-transcriptional gene expression. Their genes are either located in the extragenic space or within host genes, but these intragenic miRNA::host gene interactions are largely enigmatic. The aim of this study was to investigate the location and co-regulation of all to date available miRNA sequences and their host genes in an unbiased computational approach. The majority of miRNAs were located within intronic regions of protein-coding and non-coding genes. These intragenic miRNAs exhibited both increased target probability as well as higher target prediction scores as compared to a model of randomly permutated genes. This was associated with a higher number of miRNA recognition elements for the hosted miRNAs within their host genes. In addition, strong indirect autoregulation of host genes through modulation of functionally connected gene clusters by intragenic miRNAs was demonstrated. In addition to direct miRNA-to-host gene targeting, intragenic miRNAs also appeared to interact with functionally related genes, thus affecting their host gene function through an indirect autoregulatory mechanism. This strongly argues for the biological relevance of autoregulation not only for the host genes themselves but, more importantly, for the entire gene cluster interacting with the host gene.

SUBMITTER: Zeidler M

PROVIDER: S-EPMC7016697 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Intragenic MicroRNAs Autoregulate Their Host Genes in Both Direct and Indirect Ways-A Cross-Species Analysis.

Zeidler Maximilian M Hüttenhofer Alexander A Kress Michaela M Kummer Kai K KK

Cells 20200117 1

MicroRNAs (miRNAs) function as master switches for post-transcriptional gene expression. Their genes are either located in the extragenic space or within host genes, but these intragenic miRNA::host gene interactions are largely enigmatic. The aim of this study was to investigate the location and co-regulation of all to date available miRNA sequences and their host genes in an unbiased computational approach. The majority of miRNAs were located within intronic regions of protein-coding and non-c ...[more]

PMID: 31963421

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Project description:MicroRNAs (miRNAs) are non-coding RNAs (ncRNAs) involved in regulation of gene expression. Intragenic miRNAs, especially those exhibiting a high degree of evolutionary conservation, have been shown to be coordinately regulated and/or expressed with their host genes, either with synergistic or antagonistic correlation patterns. However, the degree of cross-species conservation of miRNA/host gene co-location is not known and co-expression information is incomplete and fragmented among several studies. Using the genomic resources (miRBase and Ensembl) we performed a genome-wide in silico screening (GWISS) for miRNA/host gene pairs in three well-annotated vertebrate species: human, mouse, and chicken. Approximately half of currently annotated miRNA genes resided within host genes: 53.0% (849/1,600) in human, 48.8% (418/855) in mouse, and 42.0% (210/499) in chicken, which we present in a central publicly available Catalog of intragenic miRNAs (http://www.integratomics-time.com/miR-host/catalog). The miRNA genes resided within either protein-coding or ncRNA genes, which include long intergenic ncRNAs (lincRNAs) and small nucleolar RNAs (snoRNAs). Twenty-seven miRNA genes were found to be located within the same host genes in all three species and the data integration from literature and databases showed that most (26/27) have been found to be co-expressed. Particularly interesting are miRNA genes located within genes encoding for miRNA silencing machinery (DGCR8, DICER1, and SND1 in human and Cnot3, Gdcr8, Eif4e, Tnrc6b, and Xpo5 in mouse). We furthermore discuss a potential for phenotype misattribution of miRNA host gene polymorphism or gene modification studies due to possible collateral effects on miRNAs hosted within them. In conclusion, the catalog of intragenic miRNAs and identified 27 miRNA/host gene pairs with cross-species conserved co-location, co-expression, and potential co-regulation, provide excellent candidates for further functional annotation of intragenic miRNAs in health and disease.

Dataset Information

Intragenic MicroRNAs Autoregulate Their Host Genes in Both Direct and Indirect Ways-A Cross-Species Analysis.

Publications

Intragenic MicroRNAs Autoregulate Their Host Genes in Both Direct and Indirect Ways-A Cross-Species Analysis.

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