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Updated: Jan 24, 2026

Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
Published on: June 24, 2021
hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles
Harry Fischl1, Jonathan Neve1, Zhiqiao Wang1
1Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Abstract:
Alternative cleavage and polyadenylation (APA) can occur at more than half of all human genes, greatly enhancing the cellular repertoire of mRNA isoforms. As these isoforms can have altered stability, localisation and coding potential, deregulation of APA can disrupt gene expression and this has been linked to many diseases including cancer progression. How APA generates cancer-specific isoform profiles and what their physiological consequences are, however, is largely unclear. Here we use a subcellular fractionation approach to determine the nuclear and cytoplasmic APA profiles of successive stages of colon cancer using a cell line-based model. Using this approach, we show that during cancer progression specific APA profiles are established. We identify that overexpression of hnRNPC has a critical role in the establishment of APA profiles characteristic for metastatic colon cancer cells, by regulating poly(A) site selection in a subset of genes that have been implicated in cancer progression including MTHFD1L.
Insights
Alternative cleavage and polyadenylation (APA) generates distinct mRNA profiles in colon cancer progression. Overexpression of hnRNPC drives metastatic cancer cell APA profiles, impacting cancer-related genes like MTHFD1L.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Alternative cleavage and polyadenylation (APA) expands the mRNA isoform repertoire, influencing gene expression.
- Deregulation of APA is linked to diseases, including cancer progression, but its role in cancer-specific isoform generation is unclear.
Purpose of the Study:
- To investigate how APA generates cancer-specific isoform profiles during colon cancer progression.
- To determine the physiological consequences of these APA profiles.
Main Methods:
- Utilized a subcellular fractionation approach.
- Analyzed nuclear and cytoplasmic APA profiles across successive stages of colon cancer using a cell line model.
Main Results:
- Demonstrated the establishment of specific APA profiles during cancer progression.
- Identified hnRNPC overexpression as critical for APA profiles in metastatic colon cancer cells.
- Showed hnRNPC regulates poly(A) site selection in cancer-associated genes, including MTHFD1L.
Conclusions:
- APA plays a significant role in shaping gene expression during colon cancer progression.
- hnRNPC is a key regulator of APA in metastatic colon cancer, affecting genes vital for cancer development.
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