primiReference: a reference for analysis of primary-microRNA expression in single-nucleus sequencing data

Amy E. Elias; Thomas A. Nuñez; Bianca Kun; Jill A. Kreiling

doi:10.1016/j.jgg.2022.10.003

Volume 50 Issue 2

Feb. 2023

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Article Navigation > Journal of Genetics and Genomics > 2023 > 50(2): 108-121

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primiReference: a reference for analysis of primary-microRNA expression in single-nucleus sequencing data

doi: 10.1016/j.jgg.2022.10.003

Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, 02903, USA

Funds:

We thank the Computational Biology Core and Center for Computation and Visualization at Brown University for their help and support throughout this project. We acknowledge and thank the Sedivy laboratory for their generous provision of materials used to conduct selected experiments. We additionally would like to acknowledge the Brunet laboratory for providing additional materials from their single-cell dataset. Support for AE was provided by T32AG041688 and P20GM119943 from the National Institutes of Health, funding for the research was provided by P20GM119943 from the National Institutes of Health.

Received Date: 2022-06-28
Accepted Date: 2022-10-24
Rev Recd Date: 2022-10-21
Publish Date: 2022-11-09

Abstract

Abstract

Single-nucleus RNA-sequencing technology has revolutionized understanding of nuanced changes in gene expression between cell types within tissues. Unfortunately, our understanding of regulatory RNAs, such as microRNAs (miRNAs), is limited through both single-cell and single-nucleus techniques due to the short length of miRNAs in the cytoplasm and the incomplete reference of longer primary miRNA (pri-miRNA) transcripts in the nucleus. We build a custom reference to align and count pri-miRNA sequences in single-nucleus data. Using young and aged subventricular zone (SVZ) nuclei, we show differential expression of pri-miRNAs targeting genes involved in neural stem cells (NSC) differentiation in the aged SVZ. Furthermore, using wild-type and 5XFAD mouse model cortex nuclei, to validate the use of primiReference, we find cell-type-specific expression of pri-miRNAs known to be involved in Alzheimer's disease (AD). pri-miRNAs likely contribute to NSC dysregulation with age and AD pathology. primiReference is paramount in capturing a global profile of gene expression and regulation in single-nucleus data and can provide key insights into cell-type-specific expression of pri-miRNAs, paving the way for future studies of regulation and pathway dysregulation. By looking at pri-miRNA abundance and transcriptional differences, regulation of gene expression by miRNAs in disease and aging can be further explored.
- Primary-microRNA,
- Aging,
- Subventricular zone,
- Alzheimer's disease,
- Single-nucleus RNA-Seq,
- microRNA,
- Transcriptomics

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References

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