scAPAdb: a comprehensive database of alternative polyadenylation at single-cell resolution

Abstract

Alternative polyadenylation (APA) is a widespread regulatory mechanism of transcript diversification in eukaryotes, which is increasingly recognized as an important layer for eukaryotic gene expression. Recent studies based on single-cell RNA-seq (scRNA-seq) have revealed cell-to-cell heterogeneity in APA usage and APA dynamics across different cell types in various tissues, biological processes and diseases. However, currently available APA databases were all collected from bulk 3′-seq and/or RNA-seq data, and no existing database has provided APA information at single-cell resolution. Here, we present a user-friendly database called scAPAdb (http://www.bmibig.cn/scAPAdb), which provides a comprehensive and manually curated atlas of poly(A) sites, APA events and poly(A) signals at the single-cell level. Currently, scAPAdb collects APA information from > 360 scRNA-seq experiments, covering six species including human, mouse and several other plant species. scAPAdb also provides batch download of data, and users can query the database through a variety of keywords such as gene identifier, gene function and accession number. scAPAdb would be a valuable and extendable resource for the study of cell-to-cell heterogeneity in APA isoform usages and APA-mediated gene regulation at the single-cell level under diverse cell types, tissues and species.

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

“…In the ‘ Nucleic acid databases ’ section, several resources illustrate the trend towards single cell-level data acquisition. Two databases cover alternative polyadenylation (APA): scAPAatlas ( 12 ) offers comprehensive analysis of human and mouse data, including correlation with gene expression and links to RNA-binding proteins or miRNAs on APA-regulated regions; scAPAdb ( 13 ) extends covered species to Arabidopsis and other plants. Elsewhere scEnhancer ( 14 ) offers a single cell perspective of enhancer regions in model organisms while scMethBank ( 15 ) covers DNA methylation in human and mouse and in healthy or cancerous cells, extending the whole organism data previously captured by the same group in MethBank ( 16 ).…”

Sites of transcription initiation drive mRNA isoform selection

“… 11 To explore the regulation of co-transcriptional processing independently of the cellular environment, we investigated 5′-3′ links at the gene level in a single tissue—the brain—in which ATSS and APA are particularly abundant. Since APA isoform usage displays cell-to-cell heterogeneity, 47 and some 3′ ends can be specific to certain cell populations, 48 we assessed whether the 5′-3′ links that we identified in Drosophila heads tend to be expressed in the same cell, or whether on the contrary, distinct isoforms are exclusive to different cell types. Using the Drosophila brain atlas, 49 we evaluated every CIA 3′ end at the single-cell level and quantified the co-occurrence of different 3′ ends of the same gene in each of the 177 cell types described in the dataset.…”

Splicing Switching of Alternative Last Exons Due to a Deletion Including Canonical Polyadenylation Site in COL6A2 Gene Causes Recessive UCMD

“…The transcript isoforms 2C2, 2C2a, and 2C2a′ of the COL6A2 gene use different final exons, resulting in alternative polyadenylation (APA) selection. Considering data from scAPAdb, 10 in addition to the transcriptome analysis results of the control case in Figure 3A , it is indicated that exon 28 in 2C2 is predominantly selected as an APA over exon 28 in 2C2a; in addition to the PAS, U or GU-rich downstream and less well-defined upstream sequence elements are known to enhance cleavage efficiency. 11 APA selection occurs when 2 or more PAS sites are present in the gene.…”