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Updated: Jan 28, 2026

Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
Published on: June 24, 2021
Temporal Splicing Switches in Elements of the TNF-Pathway Identified by Computational Analysis of Transcriptome Data
Nikolai Genov1,2, Alireza Basti3,4, Mónica Abreu5,6
1Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Theoretical Biology, 10115 Berlin, Germany. nikolai.genov@zedat.fu-berlin.de.
Abstract:
Alternative splicing plays an important role in numerous cellular processes and aberrant splice decisions are associated with cancer. Although some studies point to a regulation of alternative splicing and its effector mechanisms in a time-dependent manner, the extent and consequences of such a regulation remains poorly understood. In the present work, we investigated the time-dependent production of isoforms in two Hodgkin lymphoma cell lines of different progression stages (HD-MY-Z, stage IIIb and L-1236, stage IV) compared to a B lymphoblastoid cell line (LCL-HO) with a focus on tumour necrosis factor (TNF) pathway-related elements. For this, we used newly generated time-course RNA-sequencing data from the mentioned cell lines and applied a computational pipeline to identify genes with isoform-switching behaviour in time. We analysed the temporal profiles of the identified events and evaluated in detail the potential functional implications of alterations in isoform expression for the selected top-switching genes. Our data indicate that elements within the TNF pathway undergo a time-dependent variation in isoform production with a putative impact on cell migration, proliferation and apoptosis. These include the genes TRAF1, TNFRSF12A and NFKB2. Our results point to a role of temporal alternative splicing in isoform production, which may alter the outcome of the TNF pathway and impact on tumorigenesis.
Insights
Alternative splicing in cancer cells shows time-dependent changes, particularly in the tumor necrosis factor (TNF) pathway. These temporal isoform switches may affect cell behavior and cancer development.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- Alternative splicing is crucial for cellular processes, and its dysregulation is linked to cancer.
- The temporal regulation of alternative splicing and its impact on cancer remain largely unexplored.
Purpose of the Study:
- To investigate time-dependent isoform production in Hodgkin lymphoma cell lines.
- To focus on alterations within the tumor necrosis factor (TNF) pathway.
- To understand the functional consequences of temporal alternative splicing in tumorigenesis.
Main Methods:
- Utilized time-course RNA-sequencing data from Hodgkin lymphoma and B lymphoblastoid cell lines.
- Applied a computational pipeline to identify genes exhibiting isoform switching over time.
- Analyzed temporal expression profiles and evaluated functional implications of isoform alterations.
Main Results:
- Identified time-dependent variations in isoform production for elements within the TNF pathway.
- Observed isoform switching in key genes including TRAF1, TNFRSF12A, and NFKB2.
- Detected potential impacts on cell migration, proliferation, and apoptosis due to altered isoform expression.
Conclusions:
- Temporal alternative splicing plays a role in isoform production within the TNF pathway.
- These dynamic splicing events may influence pathway outcomes and contribute to cancer development.
- The study highlights the significance of time-dependent alternative splicing in Hodgkin lymphoma.
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