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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
...affects numerous genes involved in key cellular processes, including apoptosis, cell cycle regulation, and signal transduction (Yang et al. 2019). Specifically, HER2 alternative splicing has gained particular attention in the context of resistance to HER2-targeted therapies. HER2 splice variants have been...
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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: 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: Allele-specific alternative splicing and its functional genetic variants in human tissues
- Kofi Amoah,
- Yun-Hua Esther Hsiao,
- Jae Hoon Bahn,
- Yiwei Sun,
- Christina Burghard,
- Boon Xin Tan,
- Ei-Wen Yang,
- and Xinshu Xiao
Genome Res. March 2021 31: 359-371; Published in Advance January 15, 2021, doi:10.1101/gr.265637.120
...epigenetic or transcriptional regulation. However, it is increasingly recognized that genetic variants also play critical roles in modulating post-transcriptional mechanisms, such as alternative splicing (Wang and Cooper 2007; Sterne-Weiler and Sanford 2014).Alternative splicing is an essential mechanism...
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Research: Common cis-regulatory variation modifies the penetrance of pathogenic SHROOM3 variants in craniofacial microsomia
- Hao Zhu,
- Jiao Zhang,
- Soumya Rao,
- Matthew D. Durbin,
- Ying Li,
- Ruirui Lang,
- Jiqiang Liu,
- Baichuan Xiao,
- Hailin Shan,
- Ziqiu Meng,
- Jinmo Wang,
- Xiaokai Tang,
- Zhenni Shi,
- Liza L. Cox,
- Shouqin Zhao,
- Stephanie M. Ware,
- Tiong Y. Tan,
- Michelle de Silva,
- Lyndon Gallacher,
- Ting Liu,
- Jie Mi,
- Changqing Zeng,
- Hou-Feng Zheng,
- Qingguo Zhang,
- Stylianos E. Antonarakis,
- Timothy C. Cox,
- and Yong-Biao Zhang
Genome Res. May 2025 35: 1065-1079; Published in Advance April 15, 2025, doi:10.1101/gr.280047.124
...PMods). We additionally show that rs344131, located within a regulatory enhancer region of SHROOM3, demonstrates allele-specific effects on enhancer activity and thus impacts expression levels of the associated SHROOM3 allele harboring any rare coding variant. Our findings also suggest that CePMods may serve...
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Research: Characterization of DNA methylation reader proteins in Arabidopsis thaliana
- Jonathan Cahn,
- James P.B. Lloyd,
- Ino D. Karemaker,
- Pascal W.T.C. Jansen,
- Jahnvi Pflueger,
- Owen Duncan,
- Jakob Petereit,
- Ozren Bogdanovic,
- A. Harvey Millar,
- Michiel Vermeulen,
- and Ryan Lister
Genome Res. December 2024 34: 2229-2243; Published in Advance December 4, 2024, doi:10.1101/gr.279379.124
...no correlation (Fig. 4F). These data indicate that while mCG and many mC readers are enriched in exons, mCG does not appear to direct splicing inclusion of events in Arabidopsis seedlings, and mC readers do not direct alternative splicing.Identification of mC reader protein interactionsTo gain insights...
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Research: Hierarchical architecture of neo-sex chromosomes and accelerated adaptive evolution in tortricid moths
- Fangyuan Yang,
- Li-Jun Cao,
- Petr Nguyen,
- Zhong-Zheng Ma,
- Jin-Cui Chen,
- Wei Song,
- and Shu-Jun Wei
Genome Res. January 2025 35: 66-77; Published in Advance January 6, 2025, doi:10.1101/gr.279569.124
...of this group. This study demonstrates the association between a karyotype variant and adaptive evolution and explains the recurrent SA fusion in the Lepidoptera.Large-scale chromosomal rearrangements such as fusions may promote ecological adaptation and speciation (Guerrero and Kirkpatrick 2014; Lucek et al...
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Research: Acute depletion of METTL3 implicates N⁶-methyladenosine in alternative intron/exon inclusion in the nascent transcriptome
- Guifeng Wei,
- Mafalda Almeida,
- Greta Pintacuda,
- Heather Coker,
- Joseph S. Bowness,
- Jernej Ule,
- and Neil Brockdorff
Genome Res. August 2021 31: 1395-1408; Published in Advance June 15, 2021, doi:10.1101/gr.271635.120
...-confidence groups or random genomic regions (Fig. 2A,B). This indicated a potential role of the METTL3 complex and its methylation sites in the regulation of alternative splicing.Intronic m6A modifications correlate with RBM15 binding and H3K36me3The RNA-binding protein RBM15 plays an important role in targeting m6...
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Research: Alternative polyadenylation drives oncogenic gene expression in pancreatic ductal adenocarcinoma
- Swati Venkat,
- Arwen A. Tisdale,
- Johann R. Schwarz,
- Abdulrahman A. Alahmari,
- H. Carlo Maurer,
- Kenneth P. Olive,
- Kevin H. Eng,
- and Michael E. Feigin
Genome Res. March 2020 30: 347-360; Published in Advance February 6, 2020, doi:10.1101/gr.257550.119
...through disruption of miRNA or RNA-binding protein regulation (Elkon et al. 2013; Mayr 2016; Tian and Manley 2017). APA is driven by a large complex of polyadenylation factors that recognize a series of highly conserved sequences within the 3′ UTR on the newly synthesized pre-mRNA before cleavage...
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Research: Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation
- Jonathan Neve,
- Kaspar Burger,
- Wencheng Li,
- Mainul Hoque,
- Radhika Patel,
- Bin Tian,
- Monika Gullerova,
- and Andre Furger
Genome Res. January 2016 26: 24-35; Published in Advance November 6, 2015, doi:10.1101/gr.193995.115
...previously proposed when analyzing the conservation of APA throughout evolution (Ara et al. 2006). Perhaps in many cases, APA is the result of a fail-safe mechanism to ensure that fully transcribed and spliced transcripts obtain a mature 3′ end (Proudfoot 2011). It is possible that each CPA site has a given...
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