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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
...-term efficacy. Addressing these obstacles is vital for enhancing therapeutic strategies and patient care. Alternative splicing, a post-transcriptional mechanism that enhances transcript diversity (isoforms), can produce proteins with varied functions, cellular localizations, or binding properties. Here, we...
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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-transcriptionally...
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Method: Reference-informed prediction of alternative splicing and splicing-altering mutations from sequences
- Chencheng Xu,
- Suying Bao,
- Ye Wang,
- Wenxing Li,
- Hao Chen,
- Yufeng Shen,
- Tao Jiang,
- and Chaolin Zhang
Genome Res. July 2024 34: 1052-1065; Published in Advance July 26, 2024, doi:10.1101/gr.279044.124
..., Terrytown, NY 10591, USA; 9Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA Corresponding authors: jiang@cs.ucr.edu, cz2294@columbia.eduAbstractAlternative splicing plays a crucial role in protein diversity and gene expression regulation...
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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...by the coding region (exons and introns); and ending with a terminator and polyadenylation signals that ensure proper transcript processing and stability. Before we can determine proteins that directly regulate GOI expression, we must identify the regulatory DNA sequences relevant to the GOI such as its...
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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
..., and translation efficiency. In contrast, ALE-APA results from multiple PASs located in alternative terminal exons, which could lead to the production of truncated protein isoforms (Mariella et al. 2019; Goering et al. 2021). These alternatively polyadenylated mRNAs greatly expand the diversity of transcripts...
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Research: Transcription and potential functions of a novel XIST isoform in male peripheral glia
- Kevin S. O'Leary,
- Meng-Yen Li,
- Kevyn Jackson,
- Lijie Shi,
- Elena Ezhkova,
- Bernice E. Morrow,
- and Deyou Zheng
Genome Res. February 2026 36: 257-274; Published in Advance December 12, 2025, doi:10.1101/gr.280832.125
...integrated analyses of single-cell RNA-seq data from multiple human tissues and organs. Single-cell epigenomic data further indicate that the expression is likely driven by an alternative promoter at the end of the first exon, resulting in at least one shorter transcript (referred to as sXIST) that is active...
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Method: Kinetic measurement of gene-specific RNA polymerase II transcription elongation rates
- Haiyue Liu and
- Lea H. Gregersen
Genome Res. November 2025 35: 2550-2562; Published in Advance October 22, 2025, doi:10.1101/gr.280852.125
...(Saponaro et al. 2014). Factors involved in cotranscriptional RNA processing have also been shown to impact elongation rate. The splicing regulator SRSF2 (also known as SC35) promotes transcription elongation in a gene-specific manner (Lin et al. 2008), and U1 small nuclear ribonucleoprotein (U1 sn...
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Method: Assessing conservation of alternative splicing with evolutionary splicing graphs
- Diego Javier Zea,
- Sofya Laskina,
- Alexis Baudin,
- Hugues Richard,
- and Elodie Laine
Genome Res. August 2021 31: 1462-1473; Published in Advance June 15, 2021, doi:10.1101/gr.274696.120
...across species. We show a clear link between the functional relevance, tissue regulation, and conservation of alternative transcripts on a set of 50 genes. By scaling up to the whole human protein-coding , we identify a few thousand genes where alternative splicing modulates the number and composition...
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Research: SWATH-MS-based proteogenomic analysis reveals the involvement of alternative splicing in poplar upon lead stress
- Fu-Yuan Zhu,
- Xin Chen,
- Yu-Chen Song,
- Lydia Pui Ying Lam,
- Yuki Tobimatsu,
- Bei Gao,
- Mo-Xian Chen,
- and Fu-Liang Cao
Genome Res. March 2023 33: 371-385; Published in Advance March 24, 2023, doi:10.1101/gr.277473.122
...by our proteogenomic analysis (Supplemental Table S2), implying that these SF-associated U1 modules reciprocally regulate the AS of PtHSP70 to generate more spliced transcripts to confer Pb resistance in poplar.Conservation of AS of HSP70 orthologs in plantsTo elucidate the involvement of HSP70 in plant...
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Method: The SeqSplice multiplexed minigene splicing assay for characterization and quantitation of variant-induced BRCA1 and BRCA2 splice isoforms
- Daffodil M. Canson,
- Michael T. Parsons,
- Gemma Moir-Meyer,
- Troy Dumenil,
- Gemma Montalban,
- Erica Lin,
- Terri P. McVeigh,
- Aimee L. Davidson,
- Shaun M. Bouckaert,
- Matt Trau,
- Darren Korbie,
- and Amanda B. Spurdle
Genome Res. September 2025 35: 2104-2115; Published in Advance August 6, 2025, doi:10.1101/gr.279557.124
..., and quantitative ability of the methodology was undertaken. Initial reproducibility experiments focused on transfection with a pSPL3 vector containing wild-type (WT) BRCA2 exon 4, which was previously validated as producing no transcripts from alternative splice site usage. These results were compared to those...

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