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Science 321 (5889): 686-691

Copyright © 2008 by the American Association for the Advancement of Science

Regulation of CD45 Alternative Splicing by Heterogeneous Ribonucleoprotein, hnRNPLL

Shalini Oberdoerffer,1 Luis Ferreira Moita,2* Daniel Neems,1 Rui P. Freitas,2* Nir Hacohen,2,3 Anjana Rao1{dagger}

Abstract: The transition from naïve to activated T cells is marked by alternative splicing of pre-mRNA encoding the transmembrane phosphatase CD45. Using a short hairpin RNA interference screen, we identified heterogeneous ribonucleoprotein L-like (hnRNPLL) as a critical inducible regulator of CD45 alternative splicing. HnRNPLL was up-regulated in stimulated T cells, bound CD45 transcripts, and was both necessary and sufficient for CD45 alternative splicing. Depletion or overexpression of hnRNPLL in B and T cell lines and primary T cells resulted in reciprocal alteration of CD45RA and RO expression. Exon array analysis suggested that hnRNPLL acts as a global regulator of alternative splicing in activated T cells. Induction of hnRNPLL during hematopoietic cell activation and differentiation may allow cells to rapidly shift their transcriptomes to favor proliferation and inhibit cell death.

1 Department of Pathology, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
2 Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
3 Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

* Present address: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.

{dagger} To whom correspondence should be addressed. E-mail: arao{at}idi.harvard.edu


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