Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing

Leung, Szi Kay, Jeffries, Aaron, Castanho, Isabel, Jordan, Ben, Moore, Karen, Davies, Jonathan, Dempster, Emma, Bray, Nicholas ORCID: https://orcid.org/0000-0002-4357-574X, O'Neill, Paul, Tseng, Elizabeth, Ahmed, Zeshan, Collier, David, Jeffery, Erin, Prabhakar, Shyam, Schalkwyk, Leonard, Jops, Connor, Gandal, Michael, Sheynkman, Gloria, Hannon, Eilis and Mill, Jonathan 2021. Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing. Cell Reports 37 (7) , 110022. 10.1016/j.celrep.2021.110022

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Abstract

Alternative splicing is a post-transcriptional regulatory mechanism producing distinct mRNA molecules from a single pre-mRNA with a prominent role in the development and function of the central nervous system. We used long-read isoform sequencing to generate full-length transcript sequences in the human and mouse cortex. We identify novel transcripts not present in existing genome annotations, including transcripts mapping to putative novel (unannotated) genes and fusion transcripts incorporating exons from multiple genes. Global patterns of transcript diversity are similar between human and mouse cortex, although certain genes are characterized by striking differences between species. We also identify developmental changes in alternative splicing, with differential transcript usage between human fetal and adult cortex. Our data confirm the importance of alternative splicing in the cortex, dramatically increasing transcriptional diversity and representing an important mechanism underpinning gene regulation in the brain. We provide transcript-level data for human and mouse cortex as a resource to the scientific community.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Publisher:	Cell Press
ISSN:	2211-1247
Date of First Compliant Deposit:	3 November 2021
Date of Acceptance:	28 October 2021
Last Modified:	03 May 2023 07:20
URI:	https://orca.cardiff.ac.uk/id/eprint/145276

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