ArticleGenome research2018
A compendium of conserved cleavage and polyadenylation events in mammalian genes.
Article in Genome research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed.
- Single-cell profiling and genetic regulation of alternative polyadenylation in the human brain.Nature genetics · 2026Article
- Leveraging long read RNA-seq to decipher neuronal regulation of alternative polyadenylation.Nature communications · 2026Article
- Alternative Polyadenylation in the Brain is Modulated by Chronic Ethanol Exposure in a Sex- and Cell Type-Specific Manner.Molecular neurobiology · 2026Article
- Mechanisms of transcription termination across the coding and noncoding loci of the genome.Nature reviews. Molecular cell biology · 2026Review
- CFIm25-dependent alternative polyadenylation in AKT2 mRNA programs macrophage polarization.iScience · 2026Article
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- Modulating the cleavage and polyadenylation site: from research tools to therapeutic opportunities.RNA (New York, N.Y.) · 2026Review
- Alternative polyadenylation links RNA processing to iron metabolism in human erythropoiesis.Nucleic acids research · 2026Article
- PolyAseqTrap: a universal tool for genome-wide identification and quantification of polyadenylation sites from different 3' end sequencing data.Genome biology · 2026Article
- PolyA_DB v4: systematic polyA site identification and isoform annotation in human and mouse genomes using 3' end and long-read sequencing data.Nucleic acids research · 2026Article
- Transcription-dependent polyadenylation signal activity contributes to transcriptomic regulation during Forskolin-induced BeWo cell syncytialization.Frontiers in cell and developmental biology · 2026Article
- A Human-specific Protein Regulated by Alternative Polyadenylation Shapes Uniqueness of Human Brain Development.Genomics, proteomics & bioinformatics · 2025Article
- Single-nucleus transcriptome atlas of orbitofrontal cortex in ALS with a deep learning-based decoding of alternative polyadenylation mechanisms.Cell genomics · 2025Article
- RNA Alternative Splicing and Polyadenylation and Regulation of the Glomerular Filtration Barrier.Journal of the American Society of Nephrology : JASN · 2025Article
- NUDT21 Regulates Macrophage Cytokine Responses via Alternative Polyadenylation in ARDS.Research square · 2025Article
- Multitissue single-nucleus RNA-seq reveals cell type-specific regulatory patterns of alternative polyadenylation in pigs.Genome research · 2025Article
- Transposable element expression and sub-cellular dynamics during hPSC differentiation to endoderm, mesoderm, and ectoderm lineages.Nature communications · 2025Article
- Altered polyadenylation site usage in SERPINA1 3'UTR in response to cellular stress affects A1AT protein expression.Scientific reports · 2025Article
- IGF2BP2 binding to CPSF6 facilitates m6A-mediated alternative polyadenylation of PUM2 and promotes malignant progression in ovarian cancer.Clinical and translational medicine · 2025Article
- APALORD: An R-based tool for differential alternative polyadenylation analysis of long-read RNA-seq data.bioRxiv : the preprint server for biology · 2025Article
26 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
Cleavage and polyadenylation is essential for 3' end processing of almost all eukaryotic mRNAs. Recent studies have shown widespread alternative cleavage and polyadenylation (APA) events leading to mRNA isoforms with different 3' UTRs and/or coding sequences. Here, we present a compendium of conserved cleavage and polyadenylation sites (PASs) in mammalian genes, based on approximately 1.2 billion 3' end sequencing reads from more than 360 human, mouse, and rat samples. We show that ∼80% of mammalian mRNA genes contain at least one conserved PAS, and ∼50% have conserved APA events. PAS conservation generally reduces promiscuous 3' end processing, stabilizing gene expression levels across species. Conservation of APA correlates with gene age, gene expression features, and gene functions. Genes with certain functions, such as cell morphology, cell proliferation, and mRNA metabolism, are particularly enriched with conserved APA events. Whereas tissue-specific genes typically have a low APA rate, brain-specific genes tend to evolve APA. In addition, we show enrichment of mRNA destabilizing motifs in alternative 3' UTR sequences, leading to substantial differences in mRNA stability between 3' UTR isoforms. Using conserved PASs, we reveal sequence motifs surrounding APA sites and a preference of adenosine at the cleavage site. Furthermore, we show that mutations of U-rich motifs around the PAS often accompany APA profile differences between species. Analysis of lncRNA PASs indicates a mechanism of PAS fixation through evolution of A-rich motifs. Taken together, our results present a comprehensive view of PAS evolution in mammals, and a phylogenic perspective on APA functions.
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