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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
.... 2008; Wang et al. 2008). Alternative splicing is involved in a myriad of biological processes, including differentiation, immune cell activation, and cancer (Martinez et al. 2012; Li et al. 2014; Dvinge et al. 2016). The function of alternative splicing to diversify the proteome is vital to producing...
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Research: Pangenome analysis reveals families of ubiquitin-ligase adaptors as key genomic divergence drivers that lead to hybrid incompatibility
- Dongying Xie,
- Pohao Ye,
- Yiming Ma,
- and Zhongying Zhao
Genome Res. March 2026 36: 506-521; Published in Advance February 17, 2026, doi:10.1101/gr.280885.125
...Pan analysis reveals families of ubiquitin-ligase adaptors as key genomic divergence drivers that lead to hybrid incompatibility Dongying Xie1,2,3, Pohao Ye1,3, Yiming Ma1 and Zhongying Zhao1 1Department of Biology, Hong Kong Baptist University, Hong Kong SAR, China; 2Institute for Research...
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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
...comprehensively characterize the HER2 alternative splicing isoforms, assess their expression in primary BC patients and cell lines, and explore their role in resistance to anti-HER2 therapies. We expand the catalog of known HER2 protein-coding isoforms from 13 to 90, revealing distinct patterns of protein domains...
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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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Research: Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids
- Benjamin D. Umans and
- Yoav Gilad
Genome Res. August 2025 35: 1689-1700; Published in Advance June 2, 2025, doi:10.1101/gr.280219.124
...to stress were enriched among DE genes in both treatment conditions. For example, all oxygen-treated cell types are enriched for DE genes with roles in cellular metabolism and inflammatory responses, and most are enriched for DE genes involved in cell proliferation and DNA damage repair (Fig. 2B...
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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
...changes, especially those involving alternative splice sites with intermediate strengths, remains a challenge. This study represents an effort to improve the current state of the art with several intuitive strategies. Given the enormous complexity of splicing regulation, we used an expanded data set...
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Research: Transcriptomic landscape of transposable elements reveals LTR7-PLAAT4 as a potential oncogene and therapeutic target in pancreatic adenocarcinoma
- Meilong Shi,
- Chuanqi Teng,
- Shan Zhang,
- Xiaobo He,
- Lingyun Xu,
- Fengxian Han,
- Rongqi Wen,
- Ganjun Yu,
- Jingwen Liu,
- Yang Feng,
- Yanfeng Wu,
- Yan Ren,
- Gang Jin,
- and Jing Li
Genome Res. February 2026 36: 275-290; Published in Advance January 8, 2026, doi:10.1101/gr.280528.125
...(Fig. 5A–G; Supplemental Fig. S10). Sequence analysis revealed a robust alternative start codon within the LTR7 sequence, altering the N-terminus of isoform 2 (Supplemental Fig. S11A), which was validated by mass spectrometry following overexpression (Fig. 5H; Supplemental Fig. S11B; Huang et al. 2024...
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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
...of which occur at frequencies >20%, indicating that functional alternative splicing in S. pombe is more prevalent than previously suspected. Intron retention events make ∼80% of the cases; these events may be involved in the regulation of gene expression and, in some cases, generate novel protein isoforms...
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Research: A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
- Taylor Anglen,
- Irene M. Kaplow,
- Baekgyu Choi,
- Enya Dewars,
- Robin M. Perelli,
- Kevin T. Hagy,
- Duc Tran,
- Megan E. Ramaker,
- Svati H. Shah,
- Inkyung Jung,
- Andrew P. Landstrom,
- Ravi Karra,
- Yarui Diao,
- and Charles A. Gersbach
Genome Res. November 2025 35: 2418-2432; Published in Advance October 22, 2025, doi:10.1101/gr.280825.125
...proton leak is often a marker of oxidative stress (Vučković et al. 2022).In conclusion, R3 activation alters cellular response to stress, and activated cells are functionally distinct from control cells. R3 activation affects structural and metabolic physiology of the iPSC-CMs involved in maturation...
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Research: Mapping multitissue regulatory variants reveals a liver-centric coexpression network associated with duck egg-laying performance
- Yang Xi,
- Jingjing Qi,
- Zhao Yang,
- Yutian Zeng,
- Huicong Zhang,
- Qiuyu Tao,
- Mengru Xu,
- Anqi Huang,
- Shenqiang Hu,
- Chunchun Han,
- Lili Bai,
- Jiwei Hu,
- Jiwen Wang,
- Liang Li,
- Lingzhao Fang,
- and Hehe Liu
Genome Res. October 2025 35: 2211-2225; Published in Advance September 10, 2025, doi:10.1101/gr.280345.124
..., oviduct shell gland, and spleen, along with matched whole- sequencing data from 307 egg-laying ducks. We map cis-regulatory variants associated with gene expression (eQTL), alternative splicing (sQTL), and 3′ alternative polyadenylation (apaQTL), yielding 14,074, 6267, and 4994 genes with at least one...

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