Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes
Abstract
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
Citations
David J Wright, Nicola Hall, Naomi Irish, Angela L Man, Will Glynn, Arne Mould, Alejandro De Los Angeles, Emily Angiolini, David Swarbreck, Karim Gharbi, Elizabeth M Tunbridge, Wilfried Haerty. Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes. bioRxiv
Page last reviewed: 12 June, 2025
Metadata
Author(s): De Los Angeles, Alejandro; Mould, Arne; Tunbridge, Elizabeth
Collection: 123456789/464
Subject(s): Neuroscience
Format(s): Preprint
Date issued: 2021-04
ID: 846