Regulation of CD45 alternative splicing by heterogeneous ribonucleoprotein, hnRNPLL.
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.
Oberdoerffer
Shalini
S
Department of Pathology, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
Moita
Luis Ferreira
LF
Neems
Daniel
D
Freitas
Rui P
RP
Hacohen
Nir
N
Rao
Anjana
A
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
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