Functional interplay between RNA-binding protein HuR and microRNAs

Current Protein and Peptide Science

Volumn 13, Issue 4, 2012, Pages 372-379

  Srikantan, Subramanya ^a   Tominaga, Kumiko ^a   Gorospe, Myriam ^a  

^a NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

microRNA; mRNA decay; Post transcriptional gene regulation; Ribonucleoprotein complexes; RISC; RNA binding protein; Translational contro

Indexed keywords

AMINO ACID TRANSPORTER; CYCLOOXYGENASE 2; DNA TOPOISOMERASE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; HUR PROTEIN; MESSENGER RNA; MICRORNA; MICRORNA 125A; MICRORNA 16; MICRORNA 34A; MICRORNA 519; MICRORNA 7; MYC PROTEIN; NUCLEOLIN; PROTEIN P16; RHO FACTOR; RHOB PROTEIN; TOPOISOMERASE II ALPHA; TRANSCRIPTOME; UNCLASSIFIED DRUG;

3' UNTRANSLATED REGION; GENE CONTROL; GENE EXPRESSION; GENE TARGETING; HUMAN; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN RNA BINDING; REVIEW;

GENE EXPRESSION REGULATION; HU PARANEOPLASTIC ENCEPHALOMYELITIS ANTIGENS; HUMANS; MICRORNAS; PROTEIN BINDING; RNA, MESSENGER;

MAMMALIA;

EID: 84863927610     PISSN: 13892037     EISSN: 18755550     Source Type: Journal    
DOI: 10.2174/138920312801619394     Document Type: Review

References (75)

1. Orphanides, G.; Reinberg, D. A unified theory of gene expression. Cell, 2002, 108, 439-451.
2. Mitchell, P.; Tollervey, D. mRNA stability in eukaryotes. Curr. Opin. Genet. Dev., 2000, 10, 193-198.
3. Pullmann, R. Jr.; Kim, H.H.; Abdelmohsen, K.; Lal, A.; Martindale, J.L.; Yang, X.; Gorospe, M. Analysis of stability and translation regulatory RBP expression through binding to cognate mRNAs. Mol. Cell. Biol. 2007, 27, 6265-6278.
4. Keene, J.D. RNA regulons: coordination of post-transcriptional events. Nat. Rev. Genet., 2007, 8, 533-543.
5. Valencia-Sanchez, M.A.; Liu, J.; Hannon, G.J.; Parker, R. Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev., 2006, 20, 515-524.
6. Bartel, D.P. MicroRNAs: Target Recognition and Regulatory Functions. Cell 2009, 136, 215-233.
7. Fabian, M.R.; Sonenberg, N.; Filipowicz, W. Regulation of mRNAtranslation and stability by microRNAs. Annu. Rev. Biochem., 2010, 79, 351-379.
8. Kim, V.N.; Han, J.; Siomi, M.C. Biogenesis of small RNAs in animals. Nat. Rev. Mol. Cell. Biol., 2009, 10, 126-139
9. Newman, M.A.; Hammond, S.M. Emerging paradigms of regulated microRNA processing. Genes Dev., 2010, 24, 1086-1092
10. Vasudevan, S.; Tong, Y.; Steitz, J.A. Switching from repression to activation: microRNAs can up-regulate translation. Science, 2007, 318, 1931-1934.
11. Serva, A.; Claas, C.; Starkuviene, V.A. Potential of microRNAs for High-Content Screening. J. Nucleic Ac 2011 (ID 870903).
12. Marasa, B.S.; Srikantan, S.; Masuda, K.; Abdelmohsen, K.; Kuwano, Y.; Yang, X.; Martindale, J.L.; Rinker-Schaeffer, C.W.; Gorospe, M. Increased MKK4 abundance with replicative senescence is linked to the joint reduction of multiple microRNAs. Sci. Signal. 2009, 2(94):ra69.
13. Hinman, M.N.; Lou, H. Diverse molecular functions of Hu proteins. Cell Mol. Life Sci., 2008, 65, 3168-3181.
14. Ma, W.J.; Cheng, S.; Campbell, C.; Wright, A.; Furneaux, H. Cloning and characterization of HuR, a ubiquitously expressed Elav-like protein. J. Biol. Chem. 1996, 271, 8144-8151.
15. Mukherjee, N.; Corcoran, D.L.; Nusbaum, J.D.; Reid, D.W.; Georgiev, S.; Hafner, M.; Ascano, M. Jr.; Tuschl, T.; Ohler, U.; Keene, J.D. Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability. Mol. Cell, 2011, 43, 327-339.
16. Lebedeva, S.; Jens, M.; Theil, K.; Schwanhäusser, B.; Selbach, M.; Landthaler, M.; Rajewsky, N. Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR. Mol. Cell, 2011, 43, 340-352.
17. López de Silanes, I.; Zhan, M.; Lal, A.; Yang, X.; Gorospe, M. Identification of a target RNA motif for RNA-binding protein HuR. Proc. Natl. Acad. Sci. USA, 2004, 101, 2987-2992.
18. Abdelmohsen, K.; Kuwano, Y.; Kim, H.H.; Gorospe, M. Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: implications for cellular senescence. Biol. Chem., 2008, 389, 243-255.
19. Brennan, C.M.; Steitz, J.A. HuR and mRNA stability. Cell. Mol. Life Sci., 2001, 58, 266-277 (2001)
20. Abdelmohsen, K.; Gorospe, M. Posttranscriptional regulation of cancer traits by HuR. Wiley Interdiscip Rev. RNA, 2010, 1, 214-229.
21. Kullmann, M.; Gopfert, U.; Siewe, B.; Hengst, L. ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5'UTR. Genes Dev., 2002, 16, 3087-3099.
22. Meng, Z.; Jackson, N.L.; Choi, H.; King, P.H.; Emanuel, P.D.; Blume, S.W. Alterations in RNA-binding activities of IRESregulatory proteins as a mechanism for physiological variability and pathological dysregulation of IGF-IR translational control in human breast tumor cells. J. Cell Physiol. 2008, 217, 172-183.
23. Yeh, C.H.; Hung, L.Y.; Hsu, C.; Le, S.Y.; Lee, P.T.; Liao, W.L.; Lin, Y.T.; Chang, W.C.; Tseng, J.T. RNA-binding protein HuR interacts with thrombomodulin 5'untranslated region and represses internal ribosome entry site-mediated translation under IL-1 beta treatment. Mol. Biol. Cell., 2008, 19, 3812-3822.
24. Durie, D.; Lewis, S.M.; Liwak, U.; Kisilewicz, M.; Gorospe, M.; Holcik, M. RNA-binding protein HuR mediates cytoprotection through stimulation of XIAP translation. Oncogene, 2010, 30, 1460-1469.
25. Bhattacharyya, S.N.; Habermacher, R.; Martine, U.; Closs, E.I.; Filipowicz, W. Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell, 2006, 125, 1111-1124.
26. Kim, H.H.; Kuwano, Y.; Srikantan, S.; Lee, E.K.; Martindale, J.L.; Gorospe, M. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev., 2009, 23, 1743-1748.
27. Eberhardt, W.; Doller, A.; Pfeilschifter, J. Regulation of the mRNA-binding protein HuR by posttranslational modification: spotlight on phosphorylation. Curr. Prot. & Pept. Sci., 2012, 13,???-???.
28. Gallouzi, I.E.; Steitz, J.A. Delineation of mRNA export pathways by the use of cell-permeable peptides. Science, 2001, 294, 1895-1901.
29. Fan, X.C.; Steitz, J.A. HNS, a nuclear-cytoplasmic shuttling sequence in HuR. Proc. Natl. Acad. Sci. USA, 1998, 95, 15293-15298.
30. Güttinger, S.; Mühlhäusser, P.; Koller-Eichhorn, R.; Brennecke, J.; Kutay, U. Transportin2 functions as importin and mediates nuclear import of HuR. Proc. Natl. Acad. Sci. USA 2004, 101, 2918-2923.
31. Rebane, A.; Aab, A.; Steitz, J.A. Transportins 1 and 2 are redundant nuclear import factors for hnRNP A1 and HuR. RNA, 2004, 10, 590-599.
32. Doller, A.; Akool, E-S.; Huwiler, A.; Müller, R.; Radeke, H.H.; Pfeilschifter, J.; Eberhardt, W. Posttranslational modification of the AU-rich element binding protein HuR by protein kinase Cα elicits angiotensin II-induced stabilization and nuclear export of cyclooxygenase 2 mRNA. Mol. Cell. Biol. 2008, 28, 2608-2625.
33. Doller, A.; Huwiler, A.; Müller, R.; Radeke, H.H.; Pfeilschifter, J.; Eberhardt, W. Protein kinase C alpha-dependent phosphorylation of the mRNA-stabilizing factor HuR: implications for posttranscriptional regulation of cyclooxygenase-2. Mol. Biol. Cell, 2007, 18, 2137-2148.
34. Wang, W.; Fan, J.; Yang, X.; Fürer-Galban, S.; López de Silanes, I.; von Kobbe, C.; Guo, J.; Georas, S.N.; Foufelle, F.; Hardie, D.G.; Carling, D.; Gorospe, M. AMP-activated kinase regulates cytoplasmic HuR. Mol. Cell. Biol., 2002, 22, 3425-3436
35. Kim, H.H.; Yang, X.; Kuwano, Y.; Gorospe, M. Modification at HuR(S242) alters HuR localization and proliferative influence. Cell Cycle, 2008, 7, 3371-3377.
36. Kim, H.H.; Gorospe, M. Phosphorylated HuR shuttles in cycles. Cell Cycle 2008, 7, 3124-3126.
37. Kang, M.J.; Ryu, B.K.; Lee, M.G.; Han, J.; Lee, J.H.; Ha, T.K.; Byun, D.S.; Chae, K.S.; Lee, B.H.; Chun, H.S.; Lee, K.Y.; Kim, H.J.; Chi, S.G. NF-βB activates transcription of the RNA-binding factor HuR, via PI3K-AKT signaling, to promote gastric tumorigenesis. Gastroenterology, 2008, 135, 2030-2042.
38. Jeyaraj, S.C.; Singh, M.; Ayupova, D.A.; Govindaraju, S.; Lee, B.S. Transcriptional control of human antigen R by bone morphogenetic protein. J. Biol. Chem. 2010, 285, 4432-4440.
39. Yi, J.; Chang, N.; Liu, X.; Guo, G.; Xue, L.; Tong, T.; Gorospe, M.; Wang, W. Reduced nuclear export of HuR mRNA by HuR is linked to the loss of HuR in replicative senescence. Nucleic Acids Res. 2010, 38, 1547-1558.
40. Abdelmohsen, K.; Srikantan, S.; Yang, X.; Lal A.; Kim, H.H.; Kuwano, Y.; Galban, S.; Becker, K.G.; Kamara, D.; de Cabo, R.; Gorospe, M. Ubiquitin-mediated proteolysis of HuR by heat shock. EMBO J., 2009, 28, 1271-1282.
41. Mazroui, R.; Di Marco, S.; Clair, E.; von Roretz, C.; Tenenbaum, S.A.; Keene, J.D.; Saleh, M.; Gallouzi, I.E. Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. J. Cell Biol. 2008, 180, 113-127.
42. Masuda, K.; Abdelmohsen, K.; Kim, M.M.; Srikantan, S.; Lee, E.K.; Tominaga, K.; Selimyan, R.; Martindale, J.L.; Yang, X.; Lehrmann, E.; Zhang, Y.; Becker, K.G.; Wang, J.Y.; Kim, H.H.; Gorospe, M. Global dissociation of HuR-mRNA complexes promotes cell survival after ionizing radiation. EMBO J. 2011, 30, 1040-1053.
43. Abdelmohsen, K.; Pullmann, Jr. R.; Lal, A.; Kim, H.H.; Galban, S.; Yang, X.; Blethrow, J.D.; Walker, M.; Shubert, J.; Gillespie, D.A.; Furneaux, H.; Gorospe, M. Phosphorylation of HuR by Chk2 regulates SIRT1 expression. Mol. Cell, 2007, 25, 543-557.
44. Doller, A.; Schlepckow, K.; Schwalbe, H.; Pfeilschifter, J.; Eberhardt, W. Tandem phosphorylation of serines 221 and 318 by protein kinase Cα coordinates mRNA binding and nucleocytoplasmic shuttling of HuR. Mol. Cell. Biol., 2010, 30, 1397-1410.
45. Doller, A.; Pfeilschifter, J.; Eberhardt, W. Signalling pathways regulating nucleo-cytoplasmic shuttling of the mRNA-binding protein HuR. Cell Signal., 2008, 20, 2165-2173.
46. Lafarga, V.; Cuadrado, A.; López de Silanes, I.; Bengoechea, R.; Fernandez-Capetillo, O.; Nebreda, A.R. p38 Mitogen-activated protein kinase-and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint. Mol. Cell. Biol., 2009, 29, 4341-4351.
47. Li, H.; Park, S.; Kilburn, B.; Jelinek, M.A.; Henschen-Edman, A.; Aswad, D.W.; Stallcup, M.R.; Laird-Offringa, I.A. Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. Coactivator-associated arginine methyltransferase. J. Biol. Chem., 2002. 277, 44623-44630.
48. Kedde, M.; Agami, R. Interplay between microRNAs and RNAbinding proteins determines developmental processes. Cell Cycle, 2008, 7, 899-903.
49. Höck, J.; Weinmann, L.; Ender, C.; Rüdel, S.; Kremmer, E.; Raabe, M.; Urlaub, H.; Meister, G. Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells. EMBO Rep., 2007, 8, 1052-1060.
50. Grimson, A.; Farh, K.K.; Johnston, W.K.; Garrett-Engele, P.; Lim, L.P.; Bartel, D.P. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol. Cell, 2007, 27, 91-105.
51. Meisner, N.C.; Filipowicz, W. Properties of the Regulatory RNABinding Protein HuR and its Role in Controlling miRNA Repression. Adv. Exp. Med. Biol., 2011, 700, 106-23.
52. Srikantan, S.; Abdelmohsen, K.; Lee, E.K.; Tominaga, K.; Subaran, S.S.; Kuwano, Y.; Kulshrestha, R.; Panchakshari, R.; Kim, H.H.; Yang, X.; Martindale, J.L.; Marasa, B.; Kim, M.M.; Wersto, R.P.; Indig, F.E.; Chowdhury, D.; Gorospe, M. Translational control of Top2A influences doxorubicin efficacy. Mol. Cell. Biol., 2011, 31, 3790-801.
53. Tominaga, K.; Srikantan, S.; Lee, E.K.; Subaran, S.S.; Martindale, J.L.; Abdelmohsen, K.; Gorospe, M. Competitive regulation of Nucleolin expression by HuR and miR-494. Mol. Cell. Biol., 2011, 31, 4219-4231.
54. Wang, W.; Caldwell, M.C.; Lin, S.; Furneaux, H.; Gorospe, M. HuR regulates cyclin A and cyclin B1 mRNA stability during cell proliferation. EMBO J., 2000, 19, 2340-2350.
55. Young, L.E.; Moore, A.E.; Sokol, L.; Meisner-Kober, N.; Dixon, D.A. The mRNA Stability Factor HuR Inhibits MicroRNA-16 Targeting of Cyclooxygenase-2. Mol. Cancer Res., 2011 [Epub ahead of print]
56. Epis, M.R.; Barker, A.; Giles, K.M.; Beveridge, D.J.; Leedman, P.J. The RNA-binding protein HuR opposes the repression of ERBB-2 expression by miR-331-3p in prostate cancer cells. J. Biol. Chem., 2011 [Epub ahead of print]
57. Nielsen, C.B.; Shomron, N.; Sandberg, R.; Hornstein, E.; Kitzman, J.; Burge, C.B. Determinants of targeting by endogenous and exogenous microRNAs and siRNAs. RNA, 2007, 13, 1894-1910.
58. Glorian, V.; Maillot, G.;, Polès, S.; Iacovoni, J.S.; Favre, G.; Vagner, S. HuR-dependent loading of miRNA RISC to the mRNA encoding the Ras-related small GTPase RhoB controls its translation during UV-induced apoptosis. Cell Death Differ., 2011, 18, 1692-1701.
59. Chang, N.; Yi, J.; Guo, G.; Liu, X.; Shang, Y.; Tong, T.; Cui, Q.; Zhan, M.; Gorospe, M.; Wang, W. HuR uses AUF1 as a cofactor to promote p16INK4 mRNA decay. Mol. Cell Biol., 2010, 30, 3875-3886.
60. Merino, E.J.; Wilkinson, K.A.; Coughlan, J.L.; Weeks, K.M. RNA structure analysis at single nucleotide resolution by selective 2'-hydroxyl acylation and primer extension (SHAPE). J. Am. Chem. Soc., 2005, 127, 4223-4231.
61. Abdelmohsen, K.; Srikantan, S.; Kuwano, Y.; Gorospe, M. miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels. Proc. Natl. Acad. Sci. USA, 2008, 105, 20297-20302.
62. Marasa, B.S.; Srikantan, S.; Martindale, J.L.; Kim, M.M.; Lee, E.K.; Gorospe, M.; Abdelmohsen, K. MicroRNA profiling in human diploid fibroblasts uncovers miR-519 role in replicative senescence. Aging, 2010, 2, 333-343.
63. Abdelmohsen, K.; Kim, M.M.; Srikantan, S.; Mercken, E.M.; Brennan, S.E.; Wilson, G.M.; de Cabo, R.; Gorospe, M. miR-519 suppresses tumor growth by reducing HuR levels. Cell Cycle, 2010, 9, 1354-1359.
64. Guo, X.; Wu, Y.; Hartley, R.S. MicroRNA-125a represses cell growth by targeting HuR in breast cancer. RNA Biol., 2009, 6, 575-583.
65. Xu, F.; Zhang, X.; Lei, Y.; Liu, X.; Liu, Z.; Tong, T.; Wang, W. Loss of repression of HuR translation by miR-16 may be responsible for the elevation of HuR in human breast carcinoma. J. Cell. Biochem., 2010, 111, 727-734.
66. Jing, Q.; Huang, S.; Guth, S.; Zarubin, T.; Motoyama, A.; Chen, J.; Di Padova, F.; Lin, S.C.; Gram, H.; Han, J. Involvement of microRNA in AU-rich elementmediated mRNA instability. Cell, 2005, 120, 623-634.
67. Cimmino, A.; Calin, G.A.; Fabbri, M.; Iorio, M.V.; Ferracin, M.; Shimizu, M.; Wojcik, S.E.; Aqeilan, R.I.; Zupo, S.; Dono, M.; Rassenti, L.; Alder, H.; Volinia, S.; Liu, C.G.; Kipps, T.J.; Negrini, M.; Croce, C.M. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl. Acad. Sci. USA, 2006, 102, 13944-13949.
68. Chang, T.C.; Wentzel, E.A.; Kent, O.A.; Ramachandran, K.; Mullendore, M.; Lee, K.H.; Feldmann, G.; Yamakuchi, M.; Ferlito, M.; Lowenstein, C.J.; Arking, D.E.; Beer, M.A.; Maitra, A.; Mendell, J.T. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol. Cell, 2007, 26, 745-752.
69. Merkel, O.; Asslaber, D.; Piñón, J.D.; Egle, A.; Greil, R. Interdependent regulation of p53 and miR-34a in chronic lymphocytic leukemia. Cell Cycle, 2010, 9, 2764-2768.
70. Tarasov, V.; Jung, P.; Verdoodt, B.; Lodygin, D.; Epanchintsev, A.; Menssen, A.; Meister, G.; Hermeking, H. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle, 2007. 6, 1586-1593.
71. He, L.; He, X.; Lim, L.P.; de Stanchina, E.; Xuan, Z.; Liang, Y.; Xue, W.; Zender, L.; Magnus, J.; Ridzon, D.; Jackson, A.L.; Linsley, P.S.; Chen, C.; Lowe, S.W.; Cleary, M.A.; Hannon, G.J. A microRNA component of the p53 tumour suppressor network. Nature, 2007, 447, 1130-1134
72. Welch, C.; Chen, Y.; Stallings, R.L. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene, 2007, 26, 5017-5022.
73. Kaller, M.; Liffers, S.T.; Oeljeklaus, S.; Kuhlmann, K.; Röh, S.; Hoffmann, R.; Warscheid, B.; Hermeking, H. Genome-wide characterization of miR-34a induced changes in protein and mRNA expression by a combined pulsed SILAC and microarray analysis. Mol. Cell. Proteomics, 2011, 10, M111. 010462.
74. Kojima, K.; Fujita, Y.; Nozawa, Y.; Deguchi, T.; Ito, M. MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanisms. Prostate, 2010, 70, 1501-1512.
75. van Kouwenhove, M.; Kedde, M.; Agami, R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat. Rev. Cancer, 2011, 11, 644-656.