Full-length transcript sequencing of human and mouse cerebral cortex identifies widespread isoform diversity and alternative splicing.
Alternative Splicing
/ genetics
Animals
Brain
/ metabolism
Cerebral Cortex
/ metabolism
Exons
/ genetics
Gene Expression
/ genetics
Gene Expression Profiling
/ methods
Genome
High-Throughput Nucleotide Sequencing
/ methods
Humans
Mice
Protein Isoforms
/ genetics
RNA Precursors
/ genetics
RNA Splice Sites
/ genetics
RNA, Messenger
/ genetics
Sequence Analysis, RNA
/ methods
Transcriptome
/ genetics
isoform, transcript, expression, brain, cortex, mouse, human, adult, fetal, long-read sequencing, alternative splicing
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
16 11 2021
16 11 2021
Historique:
received:
14
10
2020
revised:
30
07
2021
accepted:
28
10
2021
entrez:
17
11
2021
pubmed:
18
11
2021
medline:
15
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34788620
pii: S2211-1247(21)01504-7
doi: 10.1016/j.celrep.2021.110022
pmc: PMC8609283
pii:
doi:
Substances chimiques
Protein Isoforms
0
RNA Precursors
0
RNA Splice Sites
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110022Subventions
Organisme : Wellcome Trust
ID : 099175/Z/12/Z
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : P50 HD103557
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R005176/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT101650MA
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH123922
Pays : United States
Organisme : Medical Research Council
ID : MR/M008924/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA044579
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH121521
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests Z.A. and D.A.C. were full-time employees of Eli Lilly & Company, Ltd., and E.T. was a full-time employee of PacBio at the time this work was performed. All other authors declare no competing interests.
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