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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
...Alternative splicing generates HER2 isoform diversity underlying antibody–drug conjugate resistance in breast cancer Gabriela D.A. Guardia1,5, Carlos H. dos Anjos1,5, Aline Rangel-Pozzo2, Filipe F. dos Santos1,3, Alexander Birbrair4, Paula F. Asprino1, Anamaria A. Camargo1 and Pedro A.F. Galante1 1...
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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
...in neurons is well established, yet few studies have examined activity-dependent alternative splicing. Alternative splicing regulates >95% of genes and is essential to diverse neuronal functions, including synapse development and calcium channel diversity. Alternative splicing is regulated by the expression...
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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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Resource: Native RNA sequencing in fission yeast reveals frequent alternative splicing isoforms
- José Carlos Montañés,
- Marta Huertas,
- Simone G. Moro,
- William R. Blevins,
- Mercè Carmona,
- José Ayté,
- Elena Hidalgo,
- and M. Mar Albà
Genome Res. June 2022 32: 1215-1227; Published in Advance May 26, 2022, doi:10.1101/gr.276516.121
...(fission yeast) retains many of the splicing features observed in humans and is thus an excellent model to study the basic mechanisms of splicing. Nearly half the genes contain introns, but the impact of alternative splicing in gene regulation and proteome diversification remains largely unexplored. Here...
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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
...expression and alternative splicing, thus impacting complex traits and phenotypes (Teng et al. 2024).Our comparative analysis across species revealed both conserved and species-specific aspects of APA regulation. In neuronal and germline cells, APA dynamics were remarkably conserved across evolution, from...
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Method: Identifying cell state–associated alternative splicing events and their coregulation
- Carlos F. Buen Abad Najar,
- Prakruthi Burra,
- Nir Yosef,
- and Liana F. Lareau
Genome Res. July 2022 32: 1385-1397; Published in Advance July 20, 2022, doi:10.1101/gr.276109.121
...splicing shapes the transcriptome and contributes to each cell's unique identity, but single-cell RNA sequencing (scRNA-seq) has struggled to capture the impact of alternative splicing. We previously showed that low recovery of mRNAs from single cells led to erroneous conclusions about the cell...
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Method: A simple method for finding related sequences by adding probabilities of alternative alignments
- Martin C. Frith
Genome Res. August 2024 34: 1165-1173; Published in Advance August 16, 2024, doi:10.1101/gr.279464.124
...sequences. Unfortunately, it is hard to tell if an alignment is likely to exist by chance. Also, the precise alignment of related regions is uncertain. One alignment does not hold all evidence that they are related. We should consider alternative alignments too. This is rarely done, because we lack a simple...
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Resource: Long-read RNA sequencing reveals widespread sex-specific alternative splicing in threespine stickleback fish
- Alice S. Naftaly,
- Shana Pau,
- and Michael A. White
Genome Res. August 2021 31: 1486-1497; Published in Advance June 15, 2021, doi:10.1101/gr.274282.120
...it possible to sequence full-length alternative transcripts, accurately characterizing alternative splicing events, alternate transcription start and end sites, and differences in UTR regions. Here, we use Pacific Biosciences (PacBio) long-read RNA-sequencing (Iso-Seq) to examine the transcriptomes of five...
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Research: Comprehensive isoform-level analysis reveals the contribution of alternative isoforms to venom evolution and repertoire diversity
- Xinhai Ye,
- Chun He,
- Yi Yang,
- Yu H. Sun,
- Shijiao Xiong,
- Kevin C. Chan,
- Yuxuan Si,
- Shan Xiao,
- Xianxin Zhao,
- Haiwei Lin,
- Yang Mei,
- Yufeng Yao,
- Gongyin Ye,
- Fei Wu,
- and Qi Fang
Genome Res. September 2023 33: 1554-1567; Published in Advance October 5, 2023, doi:10.1101/gr.277707.123
...of the venom genes generate multiple isoforms within the venom gland. Through mass spectrometry analysis, we confirm that alternative splicing contributes to the diversity of venom proteins, acting as a mechanism for expanding the venom repertoire. Notably, we identified seven venom genes that exhibit distinct...
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Research: Global regulatory features of alternative splicing across tissues and within the nervous system of C. elegans
- Bina Koterniak,
- Pallavi P. Pilaka,
- Xicotencatl Gracida,
- Lisa-Marie Schneider,
- Iva Pritišanac,
- Yun Zhang,
- and John A. Calarco
Genome Res. December 2020 30: 1766-1780; Published in Advance October 30, 2020, doi:10.1101/gr.267328.120
...a likely mechanism of splicing repression by the RNA-binding protein UNC-75/CELF via interactions with cis elements that overlap a 5′ splice site. Alternatively spliced exons also overlap more frequently with intrinsically disordered peptide regions than constitutive exons. Moreover, regulated exons...
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