Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing
Summary: 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-11-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721015047 |
| _version_ | 1818424584777498624 |
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| author | Szi Kay Leung Aaron R. Jeffries Isabel Castanho Ben T. Jordan Karen Moore Jonathan P. Davies Emma L. Dempster Nicholas J. Bray Paul O’Neill Elizabeth Tseng Zeshan Ahmed David A. Collier Erin D. Jeffery Shyam Prabhakar Leonard Schalkwyk Connor Jops Michael J. Gandal Gloria M. Sheynkman Eilis Hannon Jonathan Mill |
| author_facet | Szi Kay Leung Aaron R. Jeffries Isabel Castanho Ben T. Jordan Karen Moore Jonathan P. Davies Emma L. Dempster Nicholas J. Bray Paul O’Neill Elizabeth Tseng Zeshan Ahmed David A. Collier Erin D. Jeffery Shyam Prabhakar Leonard Schalkwyk Connor Jops Michael J. Gandal Gloria M. Sheynkman Eilis Hannon Jonathan Mill |
| author_sort | Szi Kay Leung |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-14T14:00:22Z |
| format | Article |
| id | doaj.art-1417caefb134428cac84fed4a4f86a78 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-14T14:00:22Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1417caefb134428cac84fed4a4f86a782022-12-21T22:58:43ZengElsevierCell Reports2211-12472021-11-01377110022Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicingSzi Kay Leung0Aaron R. Jeffries1Isabel Castanho2Ben T. Jordan3Karen Moore4Jonathan P. Davies5Emma L. Dempster6Nicholas J. Bray7Paul O’Neill8Elizabeth Tseng9Zeshan Ahmed10David A. Collier11Erin D. Jeffery12Shyam Prabhakar13Leonard Schalkwyk14Connor Jops15Michael J. Gandal16Gloria M. Sheynkman17Eilis Hannon18Jonathan Mill19University of Exeter, Exeter, UKUniversity of Exeter, Exeter, UKUniversity of Exeter, Exeter, UK; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USADepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USAUniversity of Exeter, Exeter, UKUniversity of Exeter, Exeter, UKUniversity of Exeter, Exeter, UKSchool of Medicine, Cardiff University, Cardiff, UKUniversity of Exeter, Exeter, UKPacific Biosciences, Menlo Park, CA, USAEli Lilly & Co., Windlesham, UKEli Lilly & Co., Windlesham, UKDepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USAGenome Institute of Singapore, Agency for Science, Technology and Research (A∗STAR), Singapore, SingaporeSchool of Life Sciences, University of Essex, Colchester, UKDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USADepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USADepartment of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; UVA Cancer Center, University of Virginia, Charlottesville, VA, USAUniversity of Exeter, Exeter, UKUniversity of Exeter, Exeter, UK; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124721015047isoform, transcript, expression, brain, cortex, mouse, human, adult, fetal, long-read sequencing, alternative splicing |
| spellingShingle | Szi Kay Leung Aaron R. Jeffries Isabel Castanho Ben T. Jordan Karen Moore Jonathan P. Davies Emma L. Dempster Nicholas J. Bray Paul O’Neill Elizabeth Tseng Zeshan Ahmed David A. Collier Erin D. Jeffery Shyam Prabhakar Leonard Schalkwyk Connor Jops Michael J. Gandal Gloria M. Sheynkman Eilis Hannon Jonathan Mill Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing Cell Reports isoform, transcript, expression, brain, cortex, mouse, human, adult, fetal, long-read sequencing, alternative splicing |
| title | Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing |
| title_full | Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing |
| title_fullStr | Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing |
| title_full_unstemmed | Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing |
| title_short | Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing |
| title_sort | full length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing |
| topic | isoform, transcript, expression, brain, cortex, mouse, human, adult, fetal, long-read sequencing, alternative splicing |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721015047 |
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