Regulation of CD45 Alternative Splicing by Heterogeneous Ribonucleoprotein, hnRNPLL Shalini Oberdoerffer, et al. Science 321, 686 (2008); DOI: 10.1126/science.1157610 The following resources related to this article are available online at www.sciencemag.org (this information is current as of February 1, 2009 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/cgi/content/full/321/5889/686 Supporting Online Material can be found at: http://www.sciencemag.org/cgi/content/full/1157610/DC1 A list of selected additional articles on the Science Web sites related to this article can be found at: http://www.sciencemag.org/cgi/content/full/321/5889/686#related-content This article cites 21 articles, 8 of which can be accessed for free: http://www.sciencemag.org/cgi/content/full/321/5889/686#otherarticles on February 1, 2009 This article has been cited by 1 article(s) on the ISI Web of Science. This article has been cited by 2 articles hosted by HighWire Press; see: http://www.sciencemag.org/cgi/content/full/321/5889/686#otherarticles This article appears in the following subject collections: Immunology http://www.sciencemag.org/cgi/collection/immunology www.sciencemag.org Information about obtaining reprints of this article or about obtaining permission to reproduce this article in whole or in part can be found at: http://www.sciencemag.org/about/permissions.dtl Downloaded from Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2008 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS. REPORTS Fig. 3. Effect of litter quality on decom- 17. H. W. Hunt et al., Biol. Fertil. Soils 3, 57 (1987). poser stoichiometry. (A) Decomposer effi- 18. W. Parton et al., Science 315, 361 (2007). 19. O. N. Krankina, M. E. Harmon, A. V. Griazkin, Can. J. For. ciency, e (left), or rCR (right) as a function r r Res. 29, 20 (1999). of L,0 when B = 0.1. Symbols indicate 20. J. B. Russell, G. M. Cook, Microbiol. Rev. 59, 48 (1995). different litter types as in Fig. 2; ◊ and ♦ 21. P. A. del Giorgio, J. J. Cole, Annu. Rev. Ecol. Syst. 29, 503 refer to a decomposing log (rB =0.122) (1998). 22. J. J. Elser et al., Nature 408, 578 (2000). and the underlying soil (rB =0.135),re- spectively [data elaborated after (16, 30)]. 23. W. J. Mattson, Annu. Rev. Ecol. Syst. 11, 119 (1980). The solid line is a linear least square fit of 24. T. J. Pandian, M. P. Marian, Freshw. Biol. 16, 93 (1986). r r r 25. F. Slansky, P. Feeny, Ecol. Monogr. 47, 209 (1977). the log-transformed CR and L,0 ( CR = 26. J. M. Craine, C. Morrow, N. Fierer, Ecology 88, 2105 0.76 0.45 × rL,0 ; R =0.88;P < 0.0001). The (2007). shaded area shows the effects on e of 27. W. B. McGill, H. W. Hunt, R. G. Woodmansee, J. O. Reuss, in Terrestrial Nitrogen Cycles: Processes, Ecosystem different rB around 0.1 (solid line). The Strategies and Management Impacts, F. E. Clark, dashed curve indicates points where rCR = r T. Rosswall, Eds. (Ecological Bulletins, Stockholm, 1981), L,0: Litter points above this curve need to vol. 33, pp. 49–115. immobilize N; points below release N 28. M. E. Harmon, Long-Term Ecological Research (LTER) since the beginning of decomposition. Intersite Litter Decomposition Experiment (LIDET), Forest (B)Estimatesofe as a function of the ratio Science Data Bank code TD023, Corvallis, OR, 2007, www.fsl.orst.edu/lter/data/abstract.cfm?dbcode=TD023. between food source N:C (rF) and consumer N:C (r )atdifferenttrophiclevels:□,ter- 29. H. L. Gholz, D. A. Wedin, S. M. Smitherman, M. E. Harmon, B W. J. Parton, Glob. Change Biol. 6, 751 (2000). restrial plant residue decomposers (this 30. S. C. Hart, G. E. Nason, D. D. Myrold, D. A. Perry, Ecology study); +, marine bacteria (21); ○,terres- 75, 880 (1994). trial larvae (25); ●, terrestrial insects (23); 31. This research was supported by Department of Energy and ×, aquatic insects (24). The solid line is a (DOE) Forest-Atmosphere Carbon Transfer and Storage linear least square fit of the log-transformed project (FACT-1), NSF DEB 0235425 and 0717191, and e r r e r r 0.60 R DOE PER 64242-0012346. LIDET data sets were provided and F/ B [ =0.43×(F/ B) ; = 0.72; by the Forest Science Data Bank, a partnership between P < 0.0001]. the Department of Forest Science, Oregon State University, and the U.S. Forest Service Pacific Northwest on February 1, 2009 Research Station, Corvallis, Oregon. Significant funding for these data was provided by the NSF Long-Term Ecological Research program (DEB-02-18088). Funding for the CIDET experiment was provided by Climate Change and Ecosystem Processes Network of the Canadian Forest Service and Natural Resources Canada Panel on Energy Research Development. We also thank G. Katul, D. Richter, and two anonymous reviewers for useful comments. establishment report,” Tech. Rep. No. BC-X-378 (Pacific poser N:C ratio is relatively constant, this pattern Supporting Online Material suggests that the decomposer communities are able Forestry Centre, Victoria, Canada, 1998). 13. See supporting materials on Science Online. www.sciencemag.org/cgi/content/full/321/5889/684/DC1 to adapt partially to low-nitrogen substrates (i.e., 14. W. J. Parton, D. S. Schimel, C. V. Cole, D. S. Ojima, Materials and Methods www.sciencemag.org Fig. S1 low rL,0) by decreasing their C-use efficiency and Soil Sci. Soc. Am. J. 51, 1173 (1987). thus the critical N:C of the litter (Fig. 3A). Such a 15. T. R. Moore, J. A. Trofymow, C. E. Prescott, J. Fyles, Table S1 pattern has been observed in aquatic environments B. D. Titus, Ecosystems (New York) 9, 46 (2006). 29 April 2008; accepted 1 July 2008 and at other trophic levels (21–25) and appears to 16. S. C. Hart, Ecology 80, 1385 (1999). 10.1126/science.1159792 be a universal response of decomposers in nutrient- poor conditions (Fig. 3B). Decreasing efficiency results in higher heterotrophic respiration per unit Regulation of CD45 Alternative mass of litter humified or unit nutrient released, Downloaded from suggesting that the soil carbon cycle is likely more open than currently thought. Splicing by Heterogeneous References and Notes Ribonucleoprotein, hnRNPLL 1. B. Berg, C. A. McClaugherty, Plant Litter: Decomposition, Humus Formation, Carbon Sequestration (Springer, 1 2 1 2 Berlin, 2003). Shalini Oberdoerffer, Luis Ferreira Moita, * Daniel Neems, Rui P. Freitas, * 2,3 1 2. M. J. Swift, O. W. Heal, J. M. Anderson, Decomposition Nir Hacohen, Anjana Rao † in Terrestrial Ecosystems, vol. 5 of Studies in Ecology (Univ. of California Press, Berkeley, 1979). The transition from naïve to activated T cells is marked by alternative splicing of pre-mRNA encoding the 3. S. A. Waksman, J. Agric. Sci. 14, 555 (1924). 4. J. D. Aber, J. M. Melillo, Can. J. Bot. 60, 2263 (1982). transmembrane phosphatase CD45. Using a short hairpin RNA interference screen, we identified 5. G. Seneviratne, Biol. Fertil. Soils 31, 60 (2000). heterogeneous ribonucleoprotein L-like (hnRNPLL) as a critical inducible regulator of CD45 alternative 6. B. Berg, G. Ekbohm, Ecology 64, 63 (1983). splicing. HnRNPLL was up-regulated in stimulated T cells, bound CD45 transcripts, and was both necessary 7. C. C. Cleveland, D. Liptzin, Biogeochemistry 85, 235 (2007). and sufficient for CD45 alternative splicing. Depletion or overexpression of hnRNPLL in B and T cell 8. R. W. Sterner, J. J. Elser, Ecological Stoichiometry: The lines and primary T cells resulted in reciprocal alteration of CD45RA and RO expression. Exon array Biology of Elements from Molecules to the Biosphere (Princeton Univ. Press, Princeton, NJ, 2002). analysis suggested that hnRNPLL acts as a global regulator of alternative splicing in activated T cells. 9. S. Manzoni, A. Porporato, Soil Biol. Biochem. 39, 1542 (2007). Induction of hnRNPLL during hematopoietic cell activation and differentiation may allow cells to rapidly 10. G. I. A˚gren, E. Bosatta, Theoretical Ecosystem Ecology: shift their transcriptomes to favor proliferation and inhibit cell death. Understanding Element Cycles (Cambridge Univ. Press, Cambridge, 1996). 1 2 11. E. Bosatta, H. Staaf, Oikos 39, 143 (1982). t is estimated that greater than 75% of genes genome ( , ). SR (serine-arginine rich) proteins 12. J. A. Trofymow, CIDET, “The Canadian Intersite yield alternative transcripts, contributing to are key positive regulators of alternative splicing Decomposition Experiment (CIDET): Project and site Iconsiderable functional diversity within the that bind enhancer sequences on nascent tran- 686 1 AUGUST 2008 VOL 321 SCIENCE www.sciencemag.org REPORTS scripts and recruit spliceosomal proteins to weak ing, thus forcing a shift of splicing to distal splice alternative splicing that culminates in increased splice sites, thereby facilitating proximal spliceo- sites (4). CD45RO and decreased CD45RA+ transcripts some assembly (3). Heterogeneous nuclear ribo- CD45 is an abundant transmembrane protein within 24 hours, and this can be blocked by nucleoproteins (hnRNPs) also regulate splicing tyrosine phosphatase expressed at the surface of cycloheximide treatment, which suggests the in- by binding negative cis-regulatory elements and T cells, B cells, and other hematopoietic cells (5). volvement of de novo protein synthesis (10). causing exon exclusion from mature mRNA (3). CD45 transcripts undergo extensive alternative To identify trans-acting factors required for SR proteins and hnRNPs function as antagonists splicing in which exons 4, 5, and 6 are variably CD45RO expression in stimulated T cells, we in alternative splicing, with binding of hnRNPs excluded (Fig.