Differential splicing across immune system lineages

Ayla Ergun, Graeme Doran, James C Costello, Henry H Paik, James J Collins, Diane Mathis, Christophe Benoist, David A Blair, Michael L Dustin, Susan A Shinton, Richard R Hardy, Tal Shay, Aviv Regev, Nadia R Cohen, Patrick J Brennan, Michael B Brenner, Francis S Kim, Tata N Rao, Amy Wagers, Tracy S P HengJeffrey A Ericson, Katherine Rothamel, Andrianna Ortiz-Lopez, Taras Kreslavsky, Anne Fletcher, Kutlu G Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon J Turley, Jennifer C Miller, Brian D Brown, Miriam Merad, Emmanuel L Gautier, Claudia V Jakubzick, Gwendalyn J Randolph, Paul Monach, Adam J Best, Jamie Knell, Ananda W Goldrath, Vladimir Jojic, Daphne Koller, David H Laidlaw, Roi Gazit, Derrick J Rossi, Nidhi Malhotra, Katelyn Sylvia, Joonsoo Kang, Natalie A Bezman, Joseph C Sun, Gundula Min-Oo, Charlie C Kim, Lewis L Lanier

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25 Citations (Scopus)

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 approximately 70 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.
Original languageEnglish
Pages (from-to)14324 - 14329
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number35
DOIs
Publication statusPublished - 2013
Externally publishedYes

Cite this

Ergun, A., Doran, G., Costello, J. C., Paik, H. H., Collins, J. J., Mathis, D., Benoist, C., Blair, D. A., Dustin, M. L., Shinton, S. A., Hardy, R. R., Shay, T., Regev, A., Cohen, N. R., Brennan, P. J., Brenner, M. B., Kim, F. S., Rao, T. N., Wagers, A., ... Lanier, L. L. (2013). Differential splicing across immune system lineages. Proceedings of the National Academy of Sciences of the United States of America, 110(35), 14324 - 14329. https://doi.org/10.1073/pnas.1311839110