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Originally published in Science Express on 10 July 2008
Science 1 August 2008:
Vol. 321. no. 5889, pp. 686 - 691
DOI: 10.1126/science.1157610
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Reports

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}

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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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Auto- and Cross-Regulation of the hnRNP L Proteins by Alternative Splicing.
O. Rossbach, L.-H. Hung, S. Schreiner, I. Grishina, M. Heiner, J. Hui, and A. Bindereif (2009)
Mol. Cell. Biol. 29, 1442-1451
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The Heterogeneous Nuclear Ribonucleoprotein L Is an Essential Component in the Ca2+/Calmodulin-dependent Protein Kinase IV-regulated Alternative Splicing through Cytidine-Adenosine Repeats.
J. Yu, Y. Hai, G. Liu, T. Fang, S. K. P. Kung, and J. Xie (2009)
J. Biol. Chem. 284, 1505-1513
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A cell-based screen for splicing regulators identifies hnRNP LL as a distinct signal-induced repressor of CD45 variable exon 4.
J. D. Topp, J. Jackson, A. A. Melton, and K. W. Lynch (2008)
RNA 14, 2038-2049
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Science. ISSN 0036-8075 (print), 1095-9203 (online)