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Open AccessArticle

Extensive Involvement of Alternative Polyadenylation in Single-Nucleus Neurons

Institute of Intelligent System and Bioinformatics, College of Automation, Harbin Engineering University, Harbin 150001, China
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Author to whom correspondence should be addressed.
Genes 2020, 11(6), 709; https://doi.org/10.3390/genes11060709
Received: 3 May 2020 / Revised: 19 June 2020 / Accepted: 25 June 2020 / Published: 26 June 2020
(This article belongs to the Section Molecular Genetics and Genomics)
Cleavage and polyadenylation are essential processes that can impact many aspects of mRNA fate. Most eukaryotic genes have alternative polyadenylation (APA) events. While the heterogeneity of mRNA polyadenylation isoform choice has been studied in specific tissues, less attention has been paid to the neuronal heterogeneity of APA selection at single-nucleus resolution. APA is highly controlled during development and neuronal activation, however, to what extent APA events vary in a specific neuronal cell population and the regulatory mechanisms are still unclear. In this paper, we investigated dynamic APA usage in different cell types using snRNA-seq data of 1424 human brain cells generated by single-cell 3′ RNA sequencing. We found that distal APA sites are not only favored by global neuronal cells, but that their usage also varies between the principal types of neuronal cell populations (excitatory neurons and inhibitory neurons). A motif analysis and a gene functional analysis indicated the enrichment of RNA-binding protein (RBP) binding sites and neuronal functions for the set of genes with neuron-enhanced distal PAS usage. Our results revealed the extensive involvement of APA regulation in neuronal populations at the single-nucleus level, providing new insights into roles for APA in specific neuronal cell populations, as well as utility in future functional studies. View Full-Text
Keywords: alternative polyadenylation; neuronal heterogeneity; snRNA-seq; RBP binding motif; neuronal populations; excitatory neurons; inhibitory neurons; APA regulation alternative polyadenylation; neuronal heterogeneity; snRNA-seq; RBP binding motif; neuronal populations; excitatory neurons; inhibitory neurons; APA regulation
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Wang, Y.; Feng, W.; Xu, S.; He, B. Extensive Involvement of Alternative Polyadenylation in Single-Nucleus Neurons. Genes 2020, 11, 709.

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