title: Regulation of CD45 alternative splicing by heterogeneous ribonucleoprotein, hnRNPLL.
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.
authors.affiliation: Department of Pathology, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Oberdoerffer
authors.forename: Luis Ferreira
authors.initials: LF
authors.lastname: Moita
authors.forename: Daniel
authors.initials: D
authors.lastname: Neems
authors.forename: Rui P
authors.initials: RP
authors.lastname: Freitas
authors.forename: Nir
authors.initials: N
authors.lastname: Hacohen
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
mesh_terms: D017398:Alternative Splicing; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000737:chemistry / Q000235:genetics*; D008213:Lymphocyte Activation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D034622:RNA Interference; D050799:STAT5 Transcription Factor / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D015854:Up-Regulation
chemical_list: C491423:HNRNPLL protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D020033:Protein Isoforms; D050799:STAT5 Transcription Factor; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D013755:Tetradecanoylphorbol Acetate