RNase L is one of the key enzymes involved in the molecular mechanisms of interferon (IFN) function. Upon binding with its activator, 5'-phosphorylated and 2'-5' linked oligoadenylates (2-5A), RNase L plays an important role in the antiviral and anti-proliferative functions of IFN, and exerts proapoptotic activity independent of IFN. These biological activities are thought to occur through the RNase L-dependent regulation of RNA stability and expression; however, the molecular targets of RNase L remain largely unknown. Recently we have found that RNase L regulates the expression of several proinflammatory genes. Our research has focused on investigating the molecular mechanism by which RNase L regulates the expression of these proinflammatory genes and the role of RNase L in inflammatory diseases.
- Nora AlghamdiPhD Student
- Dr. Huaiyu WangPost Doctoral Fellow
- Xin Yi
- Boo Seok Yun
- Chun ZengPhD Student
- Lin ZhangPhD Student
1. Huijing Yin, Aimin Zhou and Yalei Dai (2012) The association of elevated 2 5-oligoadenylate-dependent RNase L with lung cancer risk correlated deficient enzymatic activity and decreased capacity of RNase L dimerization , Lung Cancer, in press.
2. Dong J, Bu J, Du W, Li Y, Jia Y, Li J, Meng X, Yuan M, Peng X, Zhou A, Wang L (2012). A new novel mutation in FBN1 causes autosomal dominant Marfan syndrome in a Chinese family, Mol Vis. 18:81-6.
3. Yanmin Huang, Jianguo Cui, Qiaoxia Zheng, Chun Zeng, Quan Chen and Aimin Zhou (2012) 6-hydroximino-4-aza-A-homo-cholest-3-one is a potent inducer of apoptosis in cancer cells , Steroids. 77(8-9):829-34.
4. Jian Kong, Jinge Kong, Bing Pan, Shan Ke, Aimin Zhou, Lemin Zheng and WenBing Sun (2012) Insufficient radiofrequency ablation promotes angiogenesis of residual hepatocellular carcinoma via vascular endothelial growth factor , PLoS One, 7(5): e37266
5. Yi X, Zhong B, Smith KM, Geldenhuys WJ, Feng Y, Pink JJ, Dowlati A, Xu Y, Zhou A, Su B (2012) Identification of a class of novel tubulin inhibitors , J Med Chem. 55(7):3425-35.
6. Fabre O, Salehzada T, Lambert K, Yun B, Zhou A, Mercier J and Bisbal C, (2012) RNase L disruption leads to impaired adipocyte differentiation, lipids storage and insulin response , Cell Death and Differentiation,1-12.
7. Zhong B, Cai X, Chennamaneni S, Yi X, Liu L, Pink JJ, Dowlati A, Xu Y, Zhou A, Su B (2012) From COX-2 inhibitor nimesulide to potent anti-cancer agent: Synthesis, in vitro, in vivo and pharmacokinetic evaluation , Eur J Med Chem. 47(1):432-44.
8. Yanmin Huang, Jianguo Cui, Sijing Chen, Chunfang Gan and Aimin Zhou (2011) Synthesis and antiproliferative activity of some steroidal lactam compounds Steroids. 76(12):1346-50.
9. Zhong B, Cai X, Yi X, Zhou A, Chen S, Su B (2011) In vitro and in vivo effects of a cyclooxygenase-2 inhibitor nimesulide analog JCC76 in aromatase inhibitors-insensitive breast cancer cells J Steroid Biochem Mol Biol. 126(1-2):10-8.
10. Baozhong Xin, Stephen Jones, Erik G. Puffenberger, Claas Hinze, Alicia Bright, Haiyan Tan ,Aimin Zhou, Guiyun Wu, Jilda Vargus-Adams, Dimitris Agamanolis, Heng Wang (2011),A homozygous mutation in SAMHD1 gene causes cerebral vasculopathy and early onset stroke, PNAS, 108(13):5372-7.
11. Jin G, Kawsar HI, Hirsch SA, Zeng C, Jia X, Feng Z, Ghosh SK, Zheng QY, Zhou A, McIntyre TM, Weinberg A (2010), An antimicrobial peptide regulates tumor-associated macrophage trafficking via the chemokine receptor CCR2, a model for tumorigenesis. PLoS One. 8;5(6):e10993.
12. Baozhong Xin, Erik G. Puffenberger, Susan Turben, Haiyan Tan, Aimin Zhou, Heng Wang (2010), A homozygous mutation in TMCO1 causes a novel autosomal recessive syndrome characterized by craniofacial dysmorphism, skeletal anomalies and mental retardation PNAS, 107(1):258-63.
13. Jianguo Cui, Hui Wang, Yanmin Huang, Yi Xin and Aimin Zhou (2009), Synthesis and cytotoxic analysis of some disodium 3ß, 6ß-dihydroxysterol disulfates , Steroids, 74:1057-1060.
14. Jianguo Cui, Hui Wang, Yanmin Huang, Xin Yi and Aimin Zhou (2009), Synthesis and evaluation of some steroidal oximes as cytotoxic agents: Structure/Activity Studies (II) , Steroids, 74:989-995.
15. Jianguo Cui, Lei Fan, Liliang Huang, Hongli Liu, Aimin Zhou (2009) Synthesis and evaluation of some steroidal oximes as cytotoxic agents: Structure/activity studies (I) . Steroids. 74(1):62-72
16. Hongli Liu, Shu-Ling Liang, Sheetal Kumar, Crystal Weyman, Wendy Liu and Aimin Zhou (2009) Statin induces apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression Cancer Chemother Pharmacol. 63(6):997-1005.
17.Jianguo Cui, Liliang Huang, Lei fan and Aimin Zhou (2008) "A Facile and Efficient Synthesis of Some (6E)-Hydroximino-4-en-3-one Steroids, Steroidal Oximes from Cinachyrella spp. Sponges", Steroids, 73(3):252-256.
18.Yan Zhou, Crystal Weyman, Alexandru Almasan and Aimin Zhou (2008) "IFN-gamma selectively mediates cytochrome C release and apoptosis in HL-60 cells through decreased Bcl2 expression and increased Bak expression", J. Interferon & Cytokine Res., 28(2):65-72.
19.Lisam Singh, Michael Berk, Rhonda Oates, Zhenwen Zhao, Aimin Zhou, Yan Xu, (2007) "Overexpression of ovarian cancer G-protein-coupled receptor (OGR1) in prostate cancer cell induces apoptosis and inhibits cell migration", JNCI 99:1313-1327.
20.Jesper B. Andersen, Xiaoling Li, Carrieanne S. Judge, Krystyna Mazan-Mamczarz, Aimin Zhou, Longhu Zhou, Robert H. Silverman, Myriam Gorospe, and Bret A. Hassel, (2007) "Role of 2-5A dependent RNase L/HPC1 in senescence", Oncogene. 10;26(21):3081-3088.
21.Wendy Liu, Shu-Ling Liang, Hongli Liu, Robert Silverman and Aimin Zhou (2007) "Tumor suppressor function of RNase L in a mouse model", European J. of Cancer 43:202-209.
22.Shu-Ling Liang, David Quirk and Aimin Zhou (2006) "RNase L: its biological roles and regulation", IUBMB Life, 58: 1-7.
23.Shu-Ling Liang, Hongli Liu and Aimin Zhou (2006) "Lovastatin-induced apoptosis in macrophages through the Rac1/Cdc42 pathway", J. of Immunology, 177:651-656.
24.Aimin Zhou, Ross Molinaro, Krishnamurthy Malathi and Robert Silverman (2005) "Mapping of the human RNASEL promoter and expression in cancer and normal cells", J. Interferon & Cytokine Res., 25:595-603.
25.Yan Zhou, Barbara Chase, Mark Whitmore, Bryan Williams and Aimin Zhou (2005) "Double-stranded RNA-dependent protein kinase R is down-regulated by phorbol ester", Eur. J. Biochem., 272:1568-1576.
26.Beihua Dong, Quangsheng Zhou, Ji Zhao, Aimin Zhou, Ronald N Harty, Santanu Rose, Amiya Banerjee, Roger Slee, Jeanna Guenther, Bryan R.G. Willaims, Therese Wiedmer, Peter Sims and Robert H. Silverman (2004), "Enhanced Expression of Interferon Stimulated Genes by Phospholipid Scramblase 1 Suppresses Viral Replication", J. Virology, 78: 8983-8993.
27.Barbara Chase, Yan Zhou, Robert H. Silverman and Aimin Zhou (2003) "Proteasome Mediated Degradation of RNase L in Response to Phorbol-12-myristate-13-acetate (PMA) Treatment of Mouse L929 cells", J. Interferon & Cytokine Res., 23 (10): 565-573.
28.Khalid S.A. Khabar, Yunus Siddiqui, Fahad al-Zoghabi, Latifa al-Haj, Mohammed Dhalla., Aimin Zhou, Beihua Dong, Mark Whitmore, Jayashree M.Paranjape, Al-Ahdal, M., Al-Mohanna, F. Bryan R.G. Williams, and Robert H. Silverman (2003) "RNase L mediates transient control of interferon response through modulation of the double-stranded RNA dependent protein kinase PKR", J. Biol. Chem. 278(22):20124-32.
29.Wolfgang W. Leitner, Leroy N. Hwang, Michael L DeVeer, Aimin Zhou, Robert H. Silverman, Bryan R.G. Williams, Thomas W. Dubensky, Han Ying and Nicholas P. Restifo (2003) " Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways", Nature Medicine, 9:33-39.
30.Robert H. Silverman, Aimin Zhou, Michael B. Auerbach, Danielle Kish, Anton Gorbachev and Robert L. Fairchild (2002) "Skin Allograft Rejection is Suppressed in Mice Lacking the Antiviral Enzyme, 2',5'-Oligoadenylate Dependent RNase L", Viral Immunology, 15:77-83, 2002.
31.Robert Silverman, Ammar Halloum, Aimin Zhou, Beihua Dong, Fahad Al-Zoghaibi, David Kushner, Quansheng Zhou, Ji Zhao, Therese Wiedmer, and Peter J. Sims (2002) "Suppression of ovarian cancinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1", Cancer Research, 62(2):397-402.
32.Quan Chen, Bendi Gong, Aimin Zhou, Mahamad Hussein, Bryan R.G. Williams, and Alexandru Almasan (2001) "TRAIL/Apo2L induction and modulation of Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma", Blood , 98(7): 2183-2192.
33.Xiaodong Zheng, Robert H. Silverman, Aimin Zhou, Herbert E. Kaufman and James M. Hill (2001). "Mice devoid of 2-5A dependent RNase L have decreased apoptosis in cornea and increased severity of herpetic keratitis", Invest. Ophthalmol. Vis. Sci. , 42(1):120-126.
34.Lorraine Rusch, Aimin Zhou and Robert H. Silverman (2000) "Caspase-dependent apoptosis by 2',5'-oligoadenylate activation of RNase L is enhanced by IFN-beta", J. Interferon & Cytokine Res., 20:1091-1100.
35.Sangeeta Banerjee, Sungwhan An, Aimin Zhou, Robert H. Silverman and Shinji Makino (2000) "RNase L-independent specific 28S ribosomal RNA cleavage in murine coronavirus-infected cells", J. virology, 74(19):8793-8802.
36.Aimin Zhou, Huiqin Nie and Robert H. Silverman (2000), "Comparative analysis and origins of the human and murine RNase L genes that function in the antiviral action of interferon", Mammalian Genome, 11:989-992.
37.Khalid S.A. Khabar, Yunus Siddiqui, Fahad al-Zoghabi, Aimin Zhou, Sandy D. Der, Bryan R.G. and Robert H. Silverman (2000), "Viral replication and antiviral action of interferon-alpha in fibroblasts devoid of the major IFN-mediated pathways, RNase L, PKR and Mx", J. Interferon & Cytokine Res., 20:653-659.
38.Quansheng Zhou, Ji Zhao, Fahad Al-Zoghaibi, Aimin Zhou, Therese Wiedmer, Robert H. Silverman, and Peter J. Sims (2000) "Transcriptional Control of the human plasma membrane phospholipid scramblase 1 gene is mediated by interferon-alpha, Blood, 95(8):2593-2599.
39.Mikhail Iordanov, Jayashree Paranjape, Aimin Zhou, John Wong, Bryan R.G. Williams, Eliane F. Meurs, Robert H. Silverman and Bruce E. Magun (2000) "Activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase by double-stranded RNA and EMCV: Involvement of ribonuclease L, protein kinase R, and alternative pathways", Mol. Cell. Bio., 20:617-627.
40.Aimin Zhou, Jayashree M.Paranjape, Sandy Der, Brayn R.G. Williams and Robert H. Silverman (1999). "Novel innate mechanisms of interferon action are revealed in triply deficient mice", Virology, 258:435-440.
41.Sandy D. Der, Aimin Zhou, Robert H. Silverman and Bryan R.G.Williams (1998). "Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays", Proc Nat'l Acad Sci, USA 95:15623-8.
42.Aimin Zhou, Jayashree M, Paranjape,Bret A. Hassel, Huiqin Nie and Robert H. Silverman (1998). "Impact of RNase L overexpression on viral and cellular growth and death ", J. Interferon & Cytokine Res., 18:953-961.
43.Ying Xiang, David A. Simpson, Jason Spiegel, Aimin Zhou, Robert H. Silverman and Richard Condit (1998). "The Vaccinia virus A18R DNA helicase is a postreplicative negative transcription elongation factor", J. Virology, 72:7012-7023.
44.Aimin Zhou, Jayashree Paranjape, Thomas L. Brown, Huiqin Nie, Sharon Naik, Beihua Dong, Ansi Chang, Bruce Trapp, Robert Fairchild,Clemencia and Robert H. Silverman (1997). "Interferon action and apoptosis are defective in mice devoid of 2',5'-oligoadenylate dependent RNase L", EMBO, 16: 6355-6363.
45.Dibyendu N. SenGupta, Banani SenGupta, Aimin Zhou, Amitava Mitra and Robert H. Silverman (1996). "Expression of Mammalian Antiviral Enzymes from the 2-5A system in Transgenic Plants", J. Plant Bichem Biotech, 5: 69-74.
46.Aimin Zhou, L. Wang, S. Vasavada, B. Dong, H. Nie, J.M. Church, B.R.G. Williams, S. Banerjee, and R.H. Silverman (1995). "Elevated amounts of 2-5A dependent RNase in Colorectal Tumors", Clin Cancer Res, 1:1421-1428.
47.Beihua Dong, Lulu Xu, Aimin Zhou, Bret A. Hassel, Xavier Lee, Paul F. Torrence and Robert H. Silverman (1994). "Intrinsic molecular activities of the interferon-induced 2-5A dependent RNase", J. Biol. Chem., 269:14153-14158.
48.Lisa M. Baca, Peter Genis, Ganes Sen, Monte Meltzer, Aimin Zhou, Robert H. Silverman, Howard E. Gendelman (1994). "Regulation and antiviral activities of interferon inducible genes in human immunodeficiency virus infected monocyte", J. of Leukocyte Biol, 55:299-309.
49.Jeremy Squire, Aimin Zhou, Bret A. Hassel, Huiqin Nie, and Robert H. Silverman (1994)."Localization of the interferon-induced, 2-5A dependent RNase gene (RNS4) to human Chromosome 1q25 ", Genomics, 19:174-175.
50.Bret A Hassel, Aimin Zhou, Carole Sotomayor, Avuedaiappan Maran, and Robert H. Silverman (1993). " A dominant negative mutant of 2-5A dependent RNase suppresses antiproferative and antiviral effects of interferon", EMBO, 12:3297-3304.
51.Aimin Zhou, Bret A. Hassel and Robert H. Silverman (1993). "Expression cloning of 2-5A dependent RNase: a uniquely regulated mediator of interferon action", Cell, 72:753-765.
52.Paul F. Torrence, Ratan K maitra, Krystyn A. Lesiak, Aimin Zhou and Robert H Silverman (1993). "Targeting RNA for degradation with a 2-5A oligoadenylate-antisense chimera", Proc Nat'l Acad Sci, USA, 90:1300-1304.
53.Bernard Bayard and Aimin Zhou (1991)." Affinity blotting assay for 2-5A dependent nuclease", Anal Biochem, 200:108-1124.
54.Dibendy N. SenGupta, Ben Berkhout, Anne Gatignol, Aimin Zhou and Robert H. Silverman (1990). " Direct evidence for translational regulation by leader RNA and tat protein of human immunodeficiency virus type1", Proc Nat'l Acad Sci, USA, 87:7492-7496.
55.Aimin Zhou et al. "Detection of Microquantitative proteins" pp210-220 in Experimental Technology of Microbiology. Shuzheng Zhang,ed.,China science Press, 1988. (Chinese).
56.Aimin Zhou and Kaiyu Yang (1986), "Purification and characterization of 2-5A synthetase from rabbit reticulocytes", KEXUETONGBAO, 31:1259-1263 (Chinese and English).