{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T08:13:04Z","timestamp":1776240784868,"version":"3.50.1"},"reference-count":24,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5889","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:p>The transition from nai\u0308ve 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.<\/jats:p>","DOI":"10.1126\/science.1157610","type":"journal-article","created":{"date-parts":[[2008,7,11]],"date-time":"2008-07-11T01:30:57Z","timestamp":1215739857000},"page":"686-691","source":"Crossref","is-referenced-by-count":178,"title":["Regulation of CD45 Alternative Splicing by Heterogeneous Ribonucleoprotein, hnRNPLL"],"prefix":"10.1126","volume":"321","author":[{"given":"Shalini","family":"Oberdoerffer","sequence":"first","affiliation":[{"name":"Department of Pathology, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129, USA."},{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}]},{"given":"Luis Ferreira","family":"Moita","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129, USA."},{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}]},{"given":"Daniel","family":"Neems","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129, USA."},{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}]},{"given":"Rui P.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129, USA."},{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}]},{"given":"Nir","family":"Hacohen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129, USA."},{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}]},{"given":"Anjana","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Charlestown, MA 02129, USA."},{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, 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and methods are available as supporting material on Science Online."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.000505"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600745"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00419-07"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2004.03.012"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(02)00022-1"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1261\/rna.868008","volume":"14","year":"2008","unstructured":"M. J. Moore, P. A. Silver, RNA14, 197 (2008).","journal-title":"RNA"},{"key":"e_1_3_2_20_2","unstructured":"National Center for Biotechnology Information Database; www.ncbi.nlm.nih.gov\/sites\/entrez?db=gene"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.02.031"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800250105"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.15.6303-6313.2005"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1261\/rna.725208","volume":"14","year":"2008","unstructured":"L. H. Hunget al., RNA14, 284 (2008).","journal-title":"RNA"},{"key":"e_1_3_2_25_2","unstructured":"We thank A. Weiss for the JSL1 cell line E. Kieff for BJAB and BL41 cells B. North for the lentiviral expression plasmid and the RNAi Consortium at the Broad Institute for providing the plasmids to produce the splicing factor library. We thank C. Moita for assistance in assembling the library and A. Astier and D. Hafler for aid in developing the protocol for infecting and silencing genes in primary human T cells. We thank K. Eger and D. Unutmaz for the na\u00efve and activated cord blood samples. We thank J. Burke at Biotique for assistance with the array analysis. This work was supported by NIH grants CA42471 AI40127 and AI44432 to A.R. and U19 AI070352 R21 AI071060 and Defense Advanced Research Projects Agency grant W81XWH-04-C-0139 to N.H. S.O. is supported by postdoctoral training grant T32 HL066987 from the Joint Program in Transfusion Biology and Medicine Children's Hospital Boston."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1157610","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T09:06:58Z","timestamp":1704877618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1157610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8]]},"references-count":24,"journal-issue":{"issue":"5889","published-print":{"date-parts":[[2008,8]]}},"alternative-id":["10.1126\/science.1157610"],"URL":"https:\/\/doi.org\/10.1126\/science.1157610","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8]]}}}