The expression analysis of mouse interleukin-6 splice variants argued against their biological relevance
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Alternative splicing generates several interleukin-6 (IL-6) isoforms;for them an antagonistic activity to the wild-type IL-6has been proposed. In this study we quantified the relative abundance of IL-6 mRNA isoforms in a panel of mouse tissues and in C2C12 cells during myoblast differentiation or after treatment with the Ca2+ ionophore A23187, the AMP-mimetic AICAR and TNF-α. The two mouse IL-6 isoforms identified,IL-6δ5 (deletion of the first 58 bp of exon 5) and IL-6δ3(lacking exon 3), were not conserved in rat and human, did not exhibit tissue specific regulation, were expressed at low levels and their abundance closely correlated to that of full-length IL-6. Species-specific features of the IL-6 sequence,such as the presence of competitive 3’ acceptor site in exon 5and insertion of retrotransposable elements in intron 3, could explain the production of IL-6δ5 and IL-6δ3. Our results argued against biological significance for mouse IL-6 isoforms. [BMB reports 2012; 45(1): 32-37]
Abstract
Alternative splicing generates several interleukin-6 (IL-6) isoforms;for them an antagonistic activity to the wild-type IL-6has been proposed. In this study we quantified the relative abundance of IL-6 mRNA isoforms in a panel of mouse tissues and in C2C12 cells during myoblast differentiation or after treatment with the Ca2+ ionophore A23187, the AMP-mimetic AICAR and TNF-α. The two mouse IL-6 isoforms identified,IL-6δ5 (deletion of the first 58 bp of exon 5) and IL-6δ3(lacking exon 3), were not conserved in rat and human, did not exhibit tissue specific regulation, were expressed at low levels and their abundance closely correlated to that of full-length IL-6. Species-specific features of the IL-6 sequence,such as the presence of competitive 3’ acceptor site in exon 5and insertion of retrotransposable elements in intron 3, could explain the production of IL-6δ5 and IL-6δ3. Our results argued against biological significance for mouse IL-6 isoforms. [BMB reports 2012; 45(1): 32-37]
참고문헌 (25)
- Hong, D. S., "Interleukin-6 and its receptor in cancer: implications for Translational Therapeutics", Cancer, 110, pp.1911~1928 (2007)
- Simpson, R. J., "Interleukin-6: structure-function relationships", Protein Sci., 6, pp.929~955 (1997)
- Kestler, D. P., "Detection and analysis of an alternatively spliced isoform of interleukin-6 mRNA in peripheral blood mononuclear cells", Blood, 86, pp.4559~4567 (1995)
- Alberti, L., "A spliced isoform of interleukin 6 mRNA producedby renal cell carcinoma encodes for an interleukin 6 inhibitor", Cancer Res., 65, pp.2~5 (2005)
- Bihl, M. P., "Identification of a novel IL-6 isoform binding to the endogenous IL-6 receptor", Am. J. Respir. Cell. Mol. Biol., 27, pp.48~56 (2002)
- Yatsenko, O. P., "Alternative splicing of mRNA of mouse interleukin-4 and interleukin-6", Cytokine, 28, pp.190~196 (2004)
- Denessiouk, K. A., "Negative modulation of signal transduction via interleukinsplice variation", Proteins, 71, pp.751~770 (2008)
- Pedersen, B. K., "Physiological roles of muscle-derived interleukin-6 in response to exercise", Curr. Opin. Clin. Nutr. Metab. Care., 10, pp.265~271 (2007)
- Baeza-Raja, B., "p38 MAPKinduced nuclear factor-kappaB activity is required for skeletal muscle differentiation: role of interleukin-6", Mol. Biol. Cell., 15, pp.2013~2026 (2004)
- Al-Shanti, N., "Beneficial synergistic interactions of TNF-alpha andIL-6 in C2 skeletal myoblasts--potential cross-talk with IGFsystem", Growth Factors, 26, pp.61~73 (2008)
- Weigert, C., "Upregulation of IL-6 mRNA by IL-6 in skeletal muscle cells: role of IL-6 mRNA stabilization and Ca2+-dependent mechanisms", Am. J. Physiol. Cell. Physiol., 293, pp.C1139~C1147 (2007)
- Glund, S., "Role of adenosine5'-monophosphate-activated protein kinase in intreleukin-6 release from isolated mouse skeletal muscle", Endocrinology, 150, pp.600~606 (2009)
- Dreyfuss, G., "Messenger- RNA-binding proteins and the messages they carry", Nat. Rev. Mol. Cell. Biol., 3, pp.195~205 (2002)
- Serrano, A. L., "Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy", Cell. Metab., 7, pp.33~44 (2008)
- Schwartz, S., "SROOGLE: webserver for integrative, user-friendly visualization of splicing signals", Nucleic Acids Res., 37, pp.W189~W192 (2009)
- Xia, H., "Identification of alternative5'", 3' splice sites based on the mechanism of splice sitecompetition, 2006, pp.34, 6305~6313
- Meischl, C., "A new exon created by intronic insertion of a rearranged LINE-1 element as the cause of chronic granulomatous disease", Eur. J. Hum. Genet., 8, pp.697~703 (2000)
- Han, J. S., "LINE-1 retrotransposons: modulators of quantity and quality of mammalian gene expression?", Bioessays, 27, pp.775~784 (2005)
- Fox-Walsh, K. L., "Splice-site pairing is an intrinsically high fidelity process", Proc. Natl. Acad. Sci. U.S.A., 106, pp.1766~1771 (2009)
- Pan, Q., "Deep surveying of alternative splicing complexityin the human transcriptome by high-throughput sequencing", Nat. Genet., 40, pp.1413~1415 (2008)
- Melamud, E., "Stochastic noise in splicing machinery", Nucleic Acids Res., 37, pp.4873~4886 (2009)
- Hsu, S. N., "Spliceosomes walk the line: splicing errors and their impact on cellular function", RNA Biol., 6, pp.526~530 (2009)
- Sestili, P., "Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injured C2C12 murine myoblasts", Mol. Nutr. Food. Res., 53, pp.1187~1204 (2009)
- Overbergh, L., "Quantification of murine cytokine mRNAs usingreal time quantitative reverse transcriptase PCR", Cytokine, 11, pp.305~312 (1999)
- Wang, Y., "Nuclear and cytoplasmic mRNA quantification by SYBR green based real- time RT-PCR", Methods, 39, pp.356~362 (2006)