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Published Online July 10, 2008
Science DOI: 10.1126/science.1157610

Reports

Submitted on March 11, 2008
Accepted on June 20, 2008

Regulation of CD45 Alternative Splicing by Heterogeneous Ribonucleoprotein, HnRNPLL

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

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 Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA, 02129, USA.; Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.

* To whom correspondence should be addressed.
Anjana Rao , E-mail: arao{at}ibi.harvard.edu

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

The transition from naïve to activated T cells is marked by alternative splicing of pre–messenger RNA encoding the transmembrane phosphatase CD45. Using a short hairpin RNA 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 haematopoietic cell activation and differentiation may allow cells to rapidly shift their transcriptomes to favor proliferation and inhibit cell death.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)