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Resource: Multitissue single-nucleus RNA-seq reveals cell type–specific regulatory patterns of alternative polyadenylation in pigs
- Qiuhan Wen,
- Zhen Wang,
- Qi Bao,
- Tianli Ding,
- Haihan Zhang,
- Jianbo Li,
- Zhuang Liu,
- Jieping Huang,
- and Guoqiang Yi
Genome Res. September 2025 35: 2116-2129; Published in Advance June 16, 2025, doi:10.1101/gr.280095.124
...To comprehensively profile alternative polyadenylation across pig tissues, we analyzed 10x Genomics single-nucleus RNA sequencing (10x snRNA-seq) data from our previous study as a preprint on bioRxiv (Chen et al. 2023), which identified 261 cell subtypes spanning 19 distinct pig tissues (Supplemental Table S1...
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Method: Dynamics of intronic polyadenylation in the hematopoietic lineage and its regulation by DNA methylation
- Richa Rashmi,
- Abhinaya Muruganandham,
- Pranita Borkar,
- Sumana Mallick,
- Taylor Hubbs,
- Ari Aviles,
- Daniel Chung,
- and Irtisha Singh
Genome Res. April 13, 2026 gr.281044.125; Published in Advance April 13, 2026, doi:10.1101/gr.281044.125
...algorithms to accurately identify intronic polyadenylation 323 (IPA) events from bulk RNA-seq data. Unlike previous methods primarily focused on 3' UTR 324 alternative polyadenylation (APA), IPAseek robustly detects both composite and skipped IPA 325 isoforms, addressing challenges posed by complex splicing...
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Method: Delineating yeast cleavage and polyadenylation signals using deep learning
- Emily Kunce Stroup and
- Zhe Ji
Genome Res. July 2024 34: 1066-1080; Published in Advance June 24, 2024, doi:10.1101/gr.278606.123
..., thereby regulating subcellular RNA localization, translation efficiency, and stability (Tian and Manley 2017; Gruber and Zavolan 2019; Mitschka and Mayr 2022). mRNA isoforms with only a few nucleotide differences in 3′-ends can show drastic variability in RNA secondary structure and stability (Geisberg et...
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Research: Meta-analysis of activated neurons reveals dynamic regulation of diverse classes of alternative splicing
- Keegan S. Krick,
- Marissa Maroni,
- Erica Korb,
- Kristen W. Lynch,
- and Elizabeth A. Heller
Genome Res. June 2025 35: 1301-1312; Published in Advance April 24, 2025, doi:10.1101/gr.280082.124
...splicing has been linked to neurodegenerative, neurodevelopmental, and neuropsychiatric diseases (Dredge et al. 2001; Lopez Soto et al. 2019). Neuronal alternative splicing is downstream from calcium-calmodulin-dependent protein kinase (CaMK) signaling, which regulates RNA-binding proteins both post...
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Research: Alternative splicing generates HER2 isoform diversity underlying antibody–drug conjugate resistance in breast cancer
- Gabriela D.A. Guardia,
- Carlos H. dos Anjos,
- Aline Rangel-Pozzo,
- Filipe F. dos Santos,
- Alexander Birbrair,
- Paula F. Asprino,
- Anamaria A. Camargo,
- and Pedro A.F. Galante
Genome Res. September 2025 35: 1942-1958; Published in Advance July 15, 2025, doi:10.1101/gr.280304.124
...to produce multiple distinct mRNA transcripts, increasing protein diversity (Nilsen and Graveley 2010). In humans, >90% of multiexon genes undergo alternative splicing, generating roughly seven mRNA isoforms per gene on average, although only a fraction of these yield functionally distinct proteins (Pan et...
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Research: Widespread specific intron retention events in nuclear RNA complexes identified by sedimentation analysis of pluripotent cellular extracts
- Isabela T. Pereira,
- Izabela Mamede,
- Paulo P. Amaral,
- Gloria R. Franco,
- and John L. Rinn
Genome Res. October 2025 35: 2189-2198; Published in Advance August 26, 2025, doi:10.1101/gr.280431.125
...transcript abundance in cells of GETs to “All-expressed” using whole-cell RNA-seq data. The results showed that the distribution of abundance (TPM) of GETs did not differ from all other transcripts in both human (Fig. 1H) and mouse stem cells (Supplemental Fig. S3F,G). What is the subcellular localization...
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Method: Infernape uncovers cell type–specific and spatially resolved alternative polyadenylation in the brain
- Bowei Kang,
- Yalan Yang,
- Kaining Hu,
- Xiangbin Ruan,
- Yi-Lin Liu,
- Pinky Lee,
- Jasper Lee,
- Jingshu Wang,
- and Xiaochang Zhang
Genome Res. October 2023 33: 1774-1787; Published in Advance October 31, 2023, doi:10.1101/gr.277864.123
...to identify PAs from scRNA-seq and spatial data, and highlights the role of alternative PAs in neuronal gene regulation.For ∼70% of human genes, differential polyadenylation alters the 3′ untranslated regions (3′ UTRs) that may regulate mRNA metabolism and protein expression (Derti et al. 2012; Tian...
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Method: Accurate transcriptome-wide identification and quantification of alternative polyadenylation from RNA-seq data with APAIQ
- Yongkang Long,
- Bin Zhang,
- Shuye Tian,
- Jia Jia Chan,
- Juexiao Zhou,
- Zhongxiao Li,
- Yisheng Li,
- Zheng An,
- Xingyu Liao,
- Yu Wang,
- Shiwei Sun,
- Ying Xu,
- Yvonne Tay,
- Wei Chen,
- and Xin Gao
Genome Res. April 2023 33: 644-657; Published in Advance April 28, 2023, doi:10.1101/gr.277177.122
..., the transcription termination is mediated by cleavage of the nascent RNA and followed by the synthesis of non-genomic-templated polyadenosines (poly(A)) to the 3′ end of the RNA, which is known as polyadenylation. This process is controlled by a set of RNA-binding proteins (RBPs) that recognizes cis elements...
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Research: Nanopore direct RNA sequencing reveals METTL2A-mediated m³C sites in poly(A) RNA
- Shuhei Mitsutomi,
- Anzu Sugawara,
- Masahide Seki,
- Yutaka Suzuki,
- Sotaro Miyao,
- Haozhe Du,
- Kenji Takahashi,
- Yusuke Mizukami,
- Kenzui Taniue,
- and Nobuyoshi Akimitsu
Genome Res. November 2025 35: 2406-2417; Published in Advance October 30, 2025, doi:10.1101/gr.280269.124
...detected in polyadenylated (poly[A]) RNA by mass spectrometric analysis; however, its transcriptome-wide distribution and functions remain unknown because of its low abundance and technical challenges. Here, we show that METTL2A, an m3C writer, is upregulated and associated with poor prognosis...
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Research: Endonucleolytic cleavage is the primary mechanism of decay elicited by C. elegans nonsense-mediated mRNA decay
- Marcus J. Viscardi,
- Enisha Sehgal,
- and Joshua A. Arribere
Genome Res. June 2025 35: 1337-1348; Published in Advance May 9, 2025, doi:10.1101/gr.280046.124
...therapeutic efforts to control NMD. Here, we modify and deploy single-molecule nanopore mRNA sequencing to clarify the route by which NMD targets are attacked in an animal. We obtain single-molecule measures of splicing isoform, cleavage state, and poly(A) tail length. We observe robust endonucleolytic...

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