Identification and expression analysis of alternatively spliced isoforms of human interleukin-23 receptor gene in normal lymphoid cells and selected tumor cells.
Interleukin 23 (IL-23) is a new member of the IL-12 family that plays a critical role in promoting the proliferation of memory T helper 1 cells. The heterodimerized IL-23 receptor is composed of a shared IL-12 receptor beta 1 (IL-12Rbeta1) and an IL-12Rbeta2-related molecule called IL-23R. The standard form of IL-23R is encoded by at least 12 exons. Here, we demonstrate that at least six spliced isoforms of IL-23R (IL-23R1 to 6) can be generated through alternative splicing. The splicing strategies for the IL-23R gene are complicated and most often result in the deletion of exon 7 and/or exon 10. Translation prediction revealed that these spliced variants result in either premature termination to give rise to a diverse form of receptor ectodomain, or a frameshift to generate various lengths of the IL-23R endodomain. Differential expressions of IL-23R spliced variants are observed in natural killer and CD3+ CD4+ T cells. The expressions of these spliced variants are also prevalently and complicatedly regulated in tumor cell lines. Interestingly, only IL-23R2 and/or IL-23R4 variants are predominantly detected in certain human lung carcinomas, but not in their resected normal margin tissues. Thus, our results indicate that the regulation of alternative splicing on the IL-23R gene is complicated, and the preferential expression of certain IL-23R spliced variants may be a contributive factor to the pathogenesis of certain cancers.
Zhang
Xiang-Yue
XY
Department of Microbiology and Etiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
Zhang
Hai-Jing
HJ
Zhang
Yun
Y
Fu
Ying-Jie
YJ
He
Jie
J
Zhu
Li-Ping
LP
Wang
Shu-Hui
SH
Liu
Li
L
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D019295:Computational Biology; D015870:Gene Expression; D006801:Humans; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology*; D020033:Protein Isoforms / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology
C508840:IL23A protein, human; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D020033:Protein Isoforms; D018123:Receptors, Interleukin