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Research: Xist upstream deletion leads to dysregulation of Xist and autosomal gene expression
- Sudeshna Majumdar,
- Lakshmi Sowjanya Bammidi,
- Hemant C. Naik,
- Avinchal Manhas,
- Runumi Baro,
- Akash Kalita,
- Amlan Jyoti Naskar,
- Sundarraj Nidharshan,
- Girija S. Bariha,
- Dimple Notani,
- and Srimonta Gayen
Genome Res. September 2025 35: 1992-2010; Published in Advance August 6, 2025, doi:10.1101/gr.279822.124
...). From a viewpoint near the Xist transcriptional start sites, we found major contacts of the Xist with the regions encompassing Ftx loci on the inactive X in XEN cells (Fig. 1C). These interactions were found to be less in the active X Chromosome; however, we observed that Xist interacts at the 3′ region...
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Research: Dynamics and consequences of differential RNA isoform production during cardiomyocyte fate determination and early-stage maturation
- Joanna Delimata-Raczek,
- Natalia Koralewska,
- Bart Krist,
- Magdalena Rakoczy,
- Marek Figlerowicz,
- and Ireneusz Stolarek
Genome Res. April 3, 2026 gr.281150.125; Published in Advance April 3, 2026, doi:10.1101/gr.281150.125
..., we 23 delineate pervasive RNA isoform switching across the developmental trajectory of cardiac 24 differentiation. We show that the changes in isoform accumulation are largely decoupled from 25 shifts in overall gene expression levels and arise predominantly from alternative transcription 26 start...
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Resource: Isoform- and pathway-specific regulation of post-transcriptional RNA processing in human cells
- Ishwarya Venkata Narayanan,
- Karan Bedi,
- Brian Magnuson,
- Ariel McShane,
- Mario Ashaka,
- Michelle Paulsen,
- Thomas E Wilson,
- and Mats Ljungman
Genome Res. March 26, 2026 gr.280892.125; Published in Advance March 26, 2026, doi:10.1101/gr.280892.125
...174 that, on average, only about half of the splice junctions flanking introns are co-175 transcriptionally spliced, although splicing across the transcriptome becomes more 176 complete over time. This may result from either post-transcriptional splicing activities or 177 from RNA degradation...
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Method: Single-cell Rapid Capture Hybridization sequencing reliably detects isoform usage and coding mutations in targeted genes
- Hongke Peng,
- Jafar S. Jabbari,
- Luyi Tian,
- Changqing Wang,
- Yupei You,
- Chong Chyn Chua,
- Natasha S. Anstee,
- Noorul Amin,
- Andrew H. Wei,
- Nadia M. Davidson,
- Andrew W. Roberts,
- David C.S. Huang,
- Matthew E. Ritchie,
- and Rachel Thijssen
Genome Res. April 2025 35: 942-955; Published in Advance January 10, 2025, doi:10.1101/gr.279322.124
...the transcriptome profile to isoform usage, mutations, and translocations in full-length transcripts at a single-cell level (Wu and Schmitz 2023).In recent years, several high-throughput methods have been developed to enable single-cell long-read sequencing. These approaches typically involve barcoding of c...
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Method: Long-read Ribo-STAMP simultaneously measures transcription and translation with isoform resolution
- Pratibha Jagannatha,
- Alexandra T. Tankka,
- Daniel A. Lorenz,
- Tao Yu,
- Brian A. Yee,
- Kristopher W. Brannan,
- Cathy J. Zhou,
- Jason G. Underwood,
- and Gene W. Yeo
Genome Res. November 2024 34: 2012-2024; Published in Advance June 21, 2024, doi:10.1101/gr.279176.124
...Methodist Research Institute, Houston, TX 77030, USA Corresponding author: geneyeo@ucsd.eduAbstractTranscription and translation are intertwined processes in which mRNA isoforms are crucial intermediaries. However, methodological limitations in analyzing translation at the mRNA isoform level have left gaps...
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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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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
...the functionality of downstream protein products. We introduce Biosurfer, a computational approach for comparing protein isoforms, while systematically tracking the transcriptional, splicing, and translational variations that underlie differences in the sequences of the protein products. Using Biosurfer, we...
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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
...first approach the question of what regulates your GOI transcriptionally, you should start by compiling available information on chromatin landscape (especially regulatory region hallmarks) and TF binding from browsers (e.g., UCSC Genome Browser) and user-friendly databases (e.g., Harmonizome). For most...
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Method: Accurate fusion transcript identification from long- and short-read isoform sequencing at bulk or single-cell resolution
- Qian Qin,
- Victoria Popic,
- Kirsty Wienand,
- Houlin Yu,
- Emily White,
- Akanksha Khorgade,
- Asa Shin,
- Christophe Georgescu,
- Catarina D. Campbell,
- Arthur Dondi,
- Niko Beerenwinkel,
- Francisca Vazquez,
- Aziz M. Al'Khafaji,
- and Brian J. Haas
Genome Res. April 2025 35: 967-986; Published in Advance March 14, 2025, doi:10.1101/gr.279200.124
...short-read sequences. Recent advances in long-read isoform sequencing enable the detection of fusion transcripts at unprecedented resolution in bulk and single-cell samples. Here, we developed a new computational tool, CTAT-LR-Fusion, to detect fusion transcripts from long-read RNA-seq with or without...
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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
...Haiyue Liu and Lea H. Gregersen Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark Corresponding author: leag@sund.ku.dkAbstractTranscription is regulated at multiple levels, including initiation, elongation, and termination...
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