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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
...16HER2 may contribute to trastuzumab resistance (Mitra et al. 2009), whereas others have found that it may enhance sensitivity to specific HER2-targeted therapies (Castagnoli et al. 2014). Thus, the complex interplay between HER2 splicing isoforms in the context of drug response and resistance...
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Research: Global identification of mammalian host and nested gene pairs reveal tissue-specific transcriptional interplay
- Bertille Montibus,
- James A. Cain,
- Rocio T. Martinez-Nunez,
- and Rebecca J. Oakey
Genome Res. December 2024 34: 2163-2175; Published in Advance November 22, 2024, doi:10.1101/gr.279430.124
...and ∼20% of nested genes span both an intron and an exon (Supplemental Fig. S1B). The remaining overlap with exonic sequences and 3%–5% of nested genes are completely embedded within exons (Supplemental Fig. S1B). In this case, however, nested genes predominantly localized to the last exon of host genes...
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Method: Biosurfer for systematic tracking of regulatory mechanisms leading to protein isoform diversity
- Mayank Murali,
- Jamie Saquing,
- Senbao Lu,
- Ziyang Gao,
- Emily F. Watts,
- Ben Jordan,
- Zachary Peters Wakefield,
- Ana Fiszbein,
- David R. Cooper,
- Peter J. Castaldi,
- Dmitry Korkin,
- and Gloria M. Sheynkman
Genome Res. April 2025 35: 1012-1024; Published in Advance March 14, 2025, doi:10.1101/gr.279317.124
...-read RNA-seq captures long-range connectivity between multiple exons of a transcript and can reveal complex splice patterns unattainable by short-read sequencing (De Paoli‐Iseppi et al. 2021), including dependencies across distal splicing events (Anvar et al. 2018) and alternative 5′ and 3′ transcript...
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Research: Ultra-long-range interactions between active regulatory elements
- Elias T. Friman,
- Ilya M. Flyamer,
- Davide Marenduzzo,
- Shelagh Boyle,
- and Wendy A. Bickmore
Genome Res. August 2023 33: 1269-1283; Published in Advance July 14, 2023, doi:10.1101/gr.277567.122
.... Investigating factors that contribute to such chromatin interactions is therefore important for understanding gene regulation. Here, we have determined contact frequencies between millions of pairs of cis-regulatory elements from chromosome conformation capture data sets and analyzed a collection of hundreds...
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Research: GC content, but not nucleosome positioning, directly contributes to intron splicing efficiency in Paramecium
- Stefano Gnan,
- Mélody Matelot,
- Marion Weiman,
- Olivier Arnaiz,
- Frédéric Guérin,
- Linda Sperling,
- Mireille Bétermier,
- Claude Thermes,
- Chun-Long Chen,
- and Sandra Duharcourt
Genome Res. April 2022 32: 699-709; Published in Advance March 9, 2022, doi:10.1101/gr.276125.121
...repeat length of ∼151 bp, among the smallest periodicities reported. Our analysis has revealed that introns are frequently associated with inter-nucleosomal DNA, pointing to an evolutionary constraint favoring introns at the AT-rich nucleosome edge sequences. Using accurate splicing efficiency data from...
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Research: ADAR-deficiency perturbs the global splicing landscape in mouse tissues
- Utkarsh Kapoor,
- Konstantin Licht,
- Fabian Amman,
- Tobias Jakobi,
- David Martin,
- Christoph Dieterich,
- and Michael F. Jantsch
Genome Res. August 2020 30: 1107-1118; Published in Advance July 29, 2020, doi:10.1101/gr.256933.119
...the exon-intron boundary.Next, we examined if editing could have an impact on the strength of the splice sites. For this analysis, we used the MaxEntScan program that uses a maximum entropy principle to model sequence motifs near exon-intron boundaries (Yeo and Burge 2004). Specifically, it models nine...
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Research: Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences
- Arttu Jolma,
- Jilin Zhang,
- Estefania Mondragón,
- Ekaterina Morgunova,
- Teemu Kivioja,
- Kaitlin U. Laverty,
- Yimeng Yin,
- Fangjie Zhu,
- Gleb Bourenkov,
- Quaid Morris,
- Timothy R. Hughes,
- Louis James Maher III,
- and Jussi Taipale
Genome Res. July 2020 30: 962-973; Published in Advance July 23, 2020, doi:10.1101/gr.258848.119
...in human genomic sequences suggested novel roles for many RBPs. We found that three cytoplasmic proteins—ZC3H12A, ZC3H12B, and ZC3H12C—bound to motifs resembling the splice donor sequence, suggesting that these proteins are involved in degradation of cytoplasmic viral and/or unspliced transcripts...
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Research: RNA editing in nascent RNA affects pre-mRNA splicing
- Yun-Hua Esther Hsiao,
- Jae Hoon Bahn,
- Yun Yang,
- Xianzhi Lin,
- Stephen Tran,
- Ei-Wen Yang,
- Giovanni Quinones-Valdez,
- and Xinshu Xiao
Genome Res. June 2018 28: 812-823; Published in Advance May 3, 2018, doi:10.1101/gr.231209.117
...in understanding their global RNA targets and regulatory pathways. However, the interplay between individual steps of RNA processing, an essential aspect of gene regulation, remains poorly understood. By sequencing the RNA of different subcellular fractions, we examined the timing of adenosine-to-inosine (A...
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Research: In vitro iCLIP-based modeling uncovers how the splicing factor U2AF2 relies on regulation by cofactors
- F.X. Reymond Sutandy,
- Stefanie Ebersberger,
- Lu Huang,
- Anke Busch,
- Maximilian Bach,
- Hyun-Seo Kang,
- Jörg Fallmann,
- Daniel Maticzka,
- Rolf Backofen,
- Peter F. Stadler,
- Kathi Zarnack,
- Michael Sattler,
- Stefan Legewie,
- and Julian König
Genome Res. May 2018 28: 699-713; Published in Advance April 11, 2018, doi:10.1101/gr.229757.117
...regulatory hotspots at which U2AF2 binding is shaped by auxiliary factors.Focusing on different transcript regions, we observe that 75% of all U2AF2 binding sites at 3′ splice sites of constitutive exons are stabilized in vivo (Fig. 3C; Supplemental Fig. S3A). Similarly, 100% of the alternative 3′ splice...
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Method: Co-expression networks reveal the tissue-specific regulation of transcription and splicing
- Ashis Saha,
- Yungil Kim,
- Ariel D.H. Gewirtz,
- Brian Jo,
- Chuan Gao,
- Ian C. McDowell,
- The GTEx Consortium,
- Barbara E. Engelhardt,
- and Alexis Battle
Genome Res. November 2017 27: 1843-1858; Published in Advance October 11, 2017, doi:10.1101/gr.216721.116
...the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian...
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