Regulation of CD45 alternative splicing by heterogeneous ribonucleoprotein, hnRNPLL.
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Oberdoerffer S, Moita LF, Neems D, Freitas RP, Hacohen N, Rao A
Regulation of CD45 alternative splicing by heterogeneous ribonucleoprotein, hnRNPLL.
Science. 2008 Aug 1;321(5889):686-91. doi: 10.1126/science.1157610. Epub 2008 Jul 10.
- PubMed ID
- 18669861 [ View in PubMed]
- Abstract
The transition from naive 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.