Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes

Journal article

Background: Alternative splicing 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 alternative splicing 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 SH-SY5Y, and to characterise isoform expression and usage across differentiation. Results: 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 identifying candidates for future research into state change regulation. Conclusions: Our work highlights the potential of long read sequencing to uncover previously unknown transcript diversity and mechanisms influencing alternative splicing

Authors: Wright, DJ; Hall, NAL; Irish, N; Man, AL; Glynn, W

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: BMC Genomics
• Volume: 23
• Issue: 1
• Pages: 42-42
• Article number: 42
• Publication date: 2022-01-10
• DOI: 10.1186/s12864-021-08261-2
• EISSN: 1471-2164
• ISSN: 1471-2164
• Language: English
• Keywords: Gene isoform; RNA; Alternative splicing; Computational biology; Biology; Gene expression; Gene; RNA splicing; Proteomics; DNA microarray; Genetics