Abstract
The heterogeneous nuclear ribonucleoprotein C1/C2 is one of the most abundant proteins in the nucleus, and shown to have roles in cellular differentiation and proliferation through post-transcriptional regulations of certain mRNA species. We studied its role in stress response using siRNA mediated knockdown approach in HeLa cells. Upon transient transfection with plasmid encoding siRNA, the cells showed increased sensitivities to various chemical agents, namely H2O2, paraquat, camptothecin, ICRF-193 and halogenated deoxyuridines. These results demonstrate that hnRNP C1/C2 is involved in maintenance of cellular homeostasis besides cellular differentiation and proliferation.
Similar content being viewed by others
References
Dreyfuss G, Kim VN, Kataoka N (2002) Messenger-RNA-Binding proteins and the messages they carry. Nat Rev Mol Cell Biol 3:195–205
Weighardt F, Biamonti G, Silvano R (1996) The roles of heterogeneous nuclear ribonucleoproteins (hnRNP) in RNA metabolism. Bioassays 18:747–756
Burd CG, Swanson MS, Görlach M, Dreyfuss G (1989) Primary structure of the A2, B1 and C2 hnRNP proteins: a diversity of RNA binding proteins is generated by small peptide inserts. Proc Natl Acad Sci USA 86:9788–9792
McAfee JG, Shahied-Milam L, Soltaninassab SR, LeStourgeon WM (1996) A major determinant of hnRNP C protein binding to RNA is a novel bZIP-like RNA binding domain. RNA 2:1139–1152
Rech JE, LeStourgeon WM, Flicker PF (1995) Ultrastructural morphology of the hnRNP C protein tetramer. J Struct Biol 114:77–83
Barnett SF, Friedman DL, LeStourgeon WM (1989) The C proteins of HeLa 40S nuclear ribonucleoprotein particles exist as anisotropic tetramers of (C1)3 C2. Mol Cell Biol 9:492–498
Pinol-Roma S, Dreyfuss G (1992) Shuttling of pre-mRNA bindingproteins between nucleus and cytoplasm. Nature 355:730–732
Van Eekelen CA,Van Venrooij WJ (1981) hnRNA and its attachment to a nuclear protein matrix. J Cell Biol 88:554–563
Williamson DJ, Banik-Maiti S, DeGregori J, Ruley HE (2000) hnRNP C is required for postimplantation mouse development but Is dispensable for cell viability. Mol Cell Biol 20:4094–4105
Tan JH, Kajiwara Y, Shahied L, Li J, McAfee JG, LeStourgeon WM (2001) The bZIP-like motif of hnRNP C directs the nuclear accumulation of pre-mRNA and lethality in yeast. J Mol Biol 26:829–838
Michishita E, Kurahashi T, Suzuki T, Fukuda M, Fujii M, Hirano H, Ayusawa D (2002) Changes in nuclear matrix proteins during the senescence-like phenomenon induced by 5-chlorodeoxyuridine in HeLa cells. Exp Gerontol 37:885–890
Michishita E, Matsumura N, Kurahashi T, Suzuki T, Ogino H, Fujii M, Ayusawa D (2002) 5-Halogenated thymidine analogues induce a senescence-like phenomenon in HeLa cells. Biosci Biotechnol Biochem 66:877–879
Lee HH, Chien CL, Liao HK, Chen YJ,Chang ZF (2004) Nuclear efflux of heterogeneous nuclear ribonucleoprotein C1/C2 in apoptotic cells: a novel nuclear export dependent on Rho-associated kinase activation. J Cell Sci 117 Pt 23:5579–5589
Stone JR, Collins T (2002) The role of hydrogen peroxide in endothelial proliferative responses. Endothelium 9:231–238
Davies KJA (1999) The broad spectrum of responses to oxidants in proliferating cells: A new paradigm for oxidative stress. IUBMB Life 48:41–47
Burdon RH (1995) Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radical Bio Med 18:775–794
Stone JR, Maki JL, Collins T (2003) Basal and hydrogen peroxide stimulated sites of phosphorylation in heterogeneous nuclear ribonucleoprotein C1/C2. Biochemistry 42:1301–1308
Michishita E, Nakabayashi K, Suzuki T, Kaul SC, Ogino H, Fujii M, Mitsui Y, Ayusawa D (1999) 5-Bromodeoxyuridine induces senescence-like phenomena in mammalian cells regardless of cell type or species. J Biochem (Tokyo) 126:1052–1059
Liu LF (1989) DNA topoisomerase poisons as antitumor drugs. Ann Rev Biochem 58:351–375
Wang JC (1996) DNA Topoisomerases. Ann Rev Biochem 65:635–692
Muggia FM, Burris HA (1994) Clinical development of topoisomerase-interactive drugs. Adv Pharmacol 29B:1–31
Schneider E, Hsiang YH, Liu LF (1990) DNA topoisomerases as anticancer drug targets. Adv Pharmacol 21:149–183
Michishita E, Nakabayashi K, Ogino H, Suzuki T, Fujii M, Ayusawa D (1998) DNA topoisomerase inhibitors induce reversible senescence in normal human fibroblasts. Biochem Biophys Res Commun 253:667–671
He Y, Brown MA, Rothnagel JA, Saunders NA, Smith R (2005) Roles of heterogeneous nuclear ribonucleoproteins A and B in cell proliferation. J Cell Sci 118:3173Gȴ3183
Duan J, Duan J, Zhang Z, Tong T (2005) Irreversible cellular senescence induced by prolonged exposure to H2O2 involves DNA-damage-and-repair genes and telomere shortening. Intl J Biochem Cell Biol 37:1407–1420
Lee SY, Park JH, Kim S, Park EJ, Yun Y, Kwon J (2005) A proteomics approach for the identification of nucleophosmin and heterogeneous nuclear ribonucleoprotein C1/C2 as chromatin-binding proteins in response to DNA double-strand breaks. Biochem J 15:7–15
Porter SE, Champoux JJ (1989) The basis for camptothecin enhancement of DNA breakage by eukaryotic topoisomerase I. Nucleic Acids Res 17:8521–8532
Strumberg D, Pilon AA, Smith M, Hickey R, Malkas L, Pommier Y (2000) Conversion of topoisomerase I cleavage complexes on the leading strand of ribosomal DNA into 5′-phosphorylated DNA double-strand breaks by replication runoff. Mol Cell Biol 20:3977–3987
Adachi N, Suzuki H, Iiizumi S, Koyama H (2003) Hypersensitivity of nonhomologous DNA end-joining mutants to VP-16 and ICRF-193: implications for the repair of topoisomerase II-mediated DNA damage. J Biol Chem 278:35897–35902
Vagner S, Galy B, Pyronnet S (2001) Irresistible IRES attracting the translation machinery to internal ribosome entry sites. EMBO Rep 2:893–898
Holcik M, Gordon BW, Korneluk RG (2003) The internal ribosome entry site-mediated translation of antiapoptotic protein XIAP is modulated by the heterogeneous nuclear ribonucleoproteins C1 and C2. Mol Cell Biol 23:280–288
Sella O, Gerlitz G, Le SY, Elroy-Stein O (1999) Differentiation-induced internal translation of c-sis mRNA: analysis of the cis elements and their differentiation-linked binding to the hnRNP C protein. Mol Cell Biol 19:5429–5440
Kim JH, Paek KY, Choi K, Kim TD, Hahm B, Kim KT, Jang SK (2003) Heterogeneous nuclear ribonucleoprotein C modulates translation of c-myc mRNA in a cell cycle phase-dependent manner. Mol Cell Biol 23:708–720
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hossain, M.N., Fuji, M., Miki, K. et al. Downregulation of hnRNP C1/C2 by siRNA sensitizes HeLa cells to various stresses. Mol Cell Biochem 296, 151–157 (2007). https://doi.org/10.1007/s11010-006-9308-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-006-9308-2