Differential splicing across immune system lineages.
Proc Natl Acad Sci U S A
; 110(35): 14324-9, 2013 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-23934048
ABSTRACT
Alternative splicing (AS) allows increased diversity and orthogonal regulation of the transcriptional products of mammalian genomes. To assess the distribution and variation of alternative splicing across cell lineages of the immune system, we comprehensively analyzed RNA sequencing and microarray data generated by the Immunological Genome Project Consortium. AS is pervasive 60% of genes showed frequent AS isoforms in T or B lymphocytes, with 7,599 previously unreported isoforms. Distinct cell specificity was observed, with differential exon skipping in 5% of genes otherwise coexpressed in both B and T cells. The distribution of isoforms was mostly all or none, suggesting on/off switching as a frequent mode of AS regulation in lymphocytes. From the identification of differential exon use in the microarray data, clustering of exon inclusion/exclusion patterns across all Immunological Genome Project cell types showed that â¼70% of AS exons are distributed along a common pattern linked to lineage differentiation and cell cycling. Other AS events distinguished myeloid from lymphoid cells or affected only a small set of exons without clear lineage specificity (e.g., Ptprc). Computational analysis predicted specific associations between AS exons and splicing regulators, which were verified by detection of the hnRPLL/Ptprc connection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Linfócitos T
/
Processamento Alternativo
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos