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