期刊
SCIENCE
卷 321, 期 5889, 页码 686-691出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1157610
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资金
- NCI NIH HHS [R01 CA042471-23, CA42471, R01 CA042471] Funding Source: Medline
- NHLBI NIH HHS [T32 HL066987] Funding Source: Medline
- NIAID NIH HHS [R01 AI044432, R21 AI071060-02, AI40127, R01 AI044432-10, R21 AI071060, R01 AI040127-18, R01 AI044432-09, R01 AI040127, R01 AI080875, R01 AI080875-01, R21 AI071060-01, AI44432, R01 AI040127-19, U19 AI070352] Funding Source: Medline
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.
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