Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes
Alternative splicing (AS) is a key mechanism underlying cellular differentiation and a driver of complexity in mammalian neuronal tissues. However, understanding of which isoforms are differentially used or expressed and how this affects cellular differentiation remains unclear. Long read sequencing...
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Published in | bioRxiv |
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Main Authors | , , , , , , , , , , , |
Format | Paper |
Language | English |
Published |
Cold Spring Harbor
Cold Spring Harbor Laboratory Press
28.04.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Alternative splicing (AS) is a key mechanism underlying cellular differentiation and a driver of complexity in mammalian neuronal tissues. However, understanding of which isoforms are differentially used or expressed and how this affects cellular differentiation remains unclear. Long read sequencing allows full-length transcript recovery and quantification, enabling transcript-level analysis of AS processes and how these change with cell state. Here, we utilise Oxford Nanopore Technologies sequencing to produce a custom annotation of a well-studied human neuroblastoma cell line and to characterise isoform expression and usage across differentiation. We identify many previously unannotated features, including a novel transcript of the voltage-gated calcium channel subunit gene, CACNA2D2. We show differential expression and usage of transcripts during differentiation, and identify a putative molecular regulator underlying this state change. Our work highlights the potential of long read sequencing to uncover previously unknown transcript diversity and mechanisms influencing alternative splicing. Competing Interest Statement The authors have declared no competing interest. |
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DOI: | 10.1101/2021.04.27.441628 |