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Regulation of CD45 Alternative Splicing by Heterogeneous Ribonucleoprotein, hnRNPLL
Open accessAbstract
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.
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Cited by
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Gattinoni, L., Lugli, E., Ji, Y., Pos, Z., Paulos, C. M., Quigley, M. F., Almeida, J. R., Gostick, E., Yu, Z., Carpenito, C., et al. (2011) · Nature Medicine · doi:10.1038/nm.2446 · Cited by 1,974
Context-dependent control of alternative splicing by RNA-binding proteins
Fu, X.-D., & Ares, M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3778 · Cited by 1,044
CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing
Shukla, S., Kavak, E., Gregory, M., Imashimizu, M., Shutinoski, B., Kashlev, M., Oberdoerffer, P., Sandberg, R., & Oberdoerffer, S. (2011) · Nature · doi:10.1038/nature10442 · Cited by 973
Self-citationFleming, S. J., Chaffin, M. D., Arduini, A., Akkad, A.-D., Banks, E., Marioni, J. C., Philippakis, A. A., Ellinor, P. T., & Babadi, M. (2023) · Nature Methods · doi:10.1038/s41592-023-01943-7 · Cited by 867
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Metadata
- Authors
- Oberdoerffer, S., Moita, L. F., Neems, D., Freitas, R. P., Hacohen, N., & Rao, A.
- Venue
- Science
- Published
- 2008-08
- Volume
- 321
- Issue
- 5889
- Pages
- 686-691
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2098391569
- Cited by
- 205
- References
- 0
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- green
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- Oberdoerffer, S., Moita, L. F., Neems, D., Freitas, R. P., Hacohen, N., & Rao, A. (2008). Regulation of CD45 Alternative Splicing by Heterogeneous Ribonucleoprotein, hnRNPLL. Science. https://doi.org/10.1126/science.1157610
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