ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity.

作者: Michael J Moore , Nathalie E Blachere , John J Fak , Christopher Y Park , Kirsty Sawicka

DOI: 10.7554/ELIFE.33057

关键词:

摘要: Dynamic post-transcriptional control of RNA expression by RNA-binding proteins (RBPs) is critical during immune response. ZFP36 RBPs are prominent inflammatory regulators linked to autoimmunity and cancer, but functions in adaptive immunity less clear. We used HITS-CLIP define targets mouse T cells, revealing unanticipated actions regulating T-cell activation, proliferation, effector functions. Transcriptome ribosome profiling showed that represses mRNA target abundance translation, notably through novel AU-rich sites coding sequence. Functional studies revealed regulates early activation kinetics cell autonomously, attenuating marker expression, limiting expansion, promoting apoptosis. Strikingly, loss vivo accelerated responses acute viral infection enhanced anti-viral immunity. These findings uncover a role for restraining expansion functions, suggest inhibition as strategy enhance immune-based therapies.

参考文章(58)
Arvind Raghavan, Rachel L. Robison, Jennifer McNabb, Cameron R. Miller, Darlisha A. Williams, Paul R. Bohjanen, HuA and Tristetraprolin Are Induced following T Cell Activation and Display Distinct but Overlapping RNA Binding Specificities Journal of Biological Chemistry. ,vol. 276, pp. 47958- 47965 ,(2001) , 10.1074/JBC.M109511200
Yoshihiro Nakatani, Vasily Ogryzko, Immunoaffinity purification of mammalian protein complexes. Methods in Enzymology. ,vol. 370, pp. 430- 444 ,(2003) , 10.1016/S0076-6879(03)70037-8
Rachel L. Ogilvie, Michelle Abelson, Heidi H. Hau, Irina Vlasova, Perry J. Blackshear, Paul R. Bohjanen, Tristetraprolin Down-Regulates IL-2 Gene Expression through AU-Rich Element-Mediated mRNA Decay Journal of Immunology. ,vol. 174, pp. 953- 961 ,(2005) , 10.4049/JIMMUNOL.174.2.953
Dipica Haribhai, Wen Lin, Lance M. Relland, Nga Truong, Calvin B. Williams, Talal A. Chatila, Regulatory T cells dynamically control the primary immune response to foreign antigen. Journal of Immunology. ,vol. 178, pp. 2961- 2972 ,(2007) , 10.4049/JIMMUNOL.178.5.2961
Lian-Qun Qiu, Deborah J. Stumpo, Perry J. Blackshear, Myeloid-Specific Tristetraprolin Deficiency in Mice Results in Extreme Lipopolysaccharide Sensitivity in an Otherwise Minimal Phenotype Journal of Immunology. ,vol. 188, pp. 5150- 5159 ,(2012) , 10.4049/JIMMUNOL.1103700
D. Caput, B. Beutler, K. Hartog, R. Thayer, S. Brown-Shimer, A. Cerami, Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators Proceedings of the National Academy of Sciences of the United States of America. ,vol. 83, pp. 1670- 1674 ,(1986) , 10.1073/PNAS.83.6.1670
Panagiota Kafasla, Antonis Skliris, Dimitris L Kontoyiannis, Post-transcriptional coordination of immunological responses by RNA-binding proteins Nature Immunology. ,vol. 15, pp. 492- 502 ,(2014) , 10.1038/NI.2884
M.-Y. Qi, Z.-Z. Wang, Z. Zhang, Q. Shao, A. Zeng, X.-Q. Li, W.-Q. Li, C. Wang, F.-J. Tian, Q. Li, J. Zou, Y.-W. Qin, G. Brewer, S. Huang, Q. Jing, AU-Rich-Element-Dependent Translation Repression Requires the Cooperation of Tristetraprolin and RCK/P54 Molecular and Cellular Biology. ,vol. 32, pp. 913- 928 ,(2012) , 10.1128/MCB.05340-11