Differential isoform expression and alternative splicing in sex determination in mice.
Gonads
RNA-seq
Sex determination
Transcriptomics
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
12 Mar 2019
12 Mar 2019
Historique:
received:
13
11
2018
accepted:
27
02
2019
entrez:
16
3
2019
pubmed:
16
3
2019
medline:
23
8
2019
Statut:
epublish
Résumé
Alternative splicing (AS) may play an important role in gonadal sex determination (GSD) in mammals. The present study was designed to identify differentially expressed isoforms and AS modifications accompanying GSD in mice. Using deep RNA-sequencing, we performed a transcriptional analysis of XX and XY gonads during sex determination on embryonic days 11 (E11) and 12 (E12). Analysis of differentially expressed genes (DEG) identified hundreds of genes related to GSD and early sex differentiation that may represent good candidates for sex reversal. Expression at time point E11 in males was significantly enriched in RNA splicing and mRNA processing Gene Ontology terms. Differentially expressed isoform analysis identified hundreds of specific isoforms related to GSD, many of which showed no differences in the DEG analysis. Hundreds of AS events were identified as modified at E11 and E12. Female E11 gonads featured sex-biased upregulation of intron retention (in genes related to regulation of transcription, protein phosphorylation, protein transport and mRNA splicing) and exon skipping (in genes related to chromatin repression) suggesting AS as a post-transcription mechanism that controls sex determination of the bipotential fetal gonad. Our data suggests an important role of splicing regulatory mechanisms for sex determination in mice.
Sections du résumé
BACKGROUND
BACKGROUND
Alternative splicing (AS) may play an important role in gonadal sex determination (GSD) in mammals. The present study was designed to identify differentially expressed isoforms and AS modifications accompanying GSD in mice.
RESULTS
RESULTS
Using deep RNA-sequencing, we performed a transcriptional analysis of XX and XY gonads during sex determination on embryonic days 11 (E11) and 12 (E12). Analysis of differentially expressed genes (DEG) identified hundreds of genes related to GSD and early sex differentiation that may represent good candidates for sex reversal. Expression at time point E11 in males was significantly enriched in RNA splicing and mRNA processing Gene Ontology terms. Differentially expressed isoform analysis identified hundreds of specific isoforms related to GSD, many of which showed no differences in the DEG analysis. Hundreds of AS events were identified as modified at E11 and E12. Female E11 gonads featured sex-biased upregulation of intron retention (in genes related to regulation of transcription, protein phosphorylation, protein transport and mRNA splicing) and exon skipping (in genes related to chromatin repression) suggesting AS as a post-transcription mechanism that controls sex determination of the bipotential fetal gonad.
CONCLUSION
CONCLUSIONS
Our data suggests an important role of splicing regulatory mechanisms for sex determination in mice.
Identifiants
pubmed: 30871468
doi: 10.1186/s12864-019-5572-x
pii: 10.1186/s12864-019-5572-x
pmc: PMC6419433
doi:
Substances chimiques
Biomarkers
0
Protein Isoforms
0
Types de publication
Journal Article
Langues
eng
Pagination
202Subventions
Organisme : Ministerio de Economía, Industria y Competitividad, Gobierno de España
ID : AGL2015-66145
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : REP-BIOTECH 675526
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