Extensive alternative splicing of interleukin-7 in malignant hematopoietic cells: implication of distinct isoforms in modulating IL-7 activity
| Autor: | Birgit Beyermann, Karlheinz Seeger, Alexander Korte, Joachim Köchling, Christian Kebelmann-Betzing, Anja Möricke, Tillmann Taube, Günter Henze |
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| Rok vydání: | 1999 |
| Předmět: |
Gene isoform
Reverse Transcriptase Polymerase Chain Reaction T cell Interleukin-7 Immunology Alternative splicing Interleukin Cell Biology Biology Precursor Cell Lymphoblastic Leukemia-Lymphoma Molecular biology Burkitt Lymphoma Cell biology Haematopoiesis Alternative Splicing Open Reading Frames medicine.anatomical_structure Genetic Code Virology medicine Tumor Cells Cultured Humans Protein Isoforms RNA Messenger Child |
| Zdroj: | Journal of interferoncytokine research : the official journal of the International Society for Interferon and Cytokine Research. 19(5) |
| ISSN: | 1079-9907 |
| Popis: | Interleukin-7 (IL-7) plays a pivotal role in early stages of normal B and T cell development. In addition, IL-7 stimulates the proliferation of both antitumor reactive cells and a number of T and B cell malignancies, underlining its significance for leukemogenesis. However, its exact role in the process of pathologic maturation of lymphocytes and regulation of the immune response is not completely understood. As alternative splicing of pre-mRNA has been shown to be involved in the control of gene expression, and splicing-derived protein isoforms with antagonistic activity have been found, we assessed the mRNA-expression of IL-7 and its previously described alternative splice variant lacking exon 4, IL-7delta4, in leukemic cells from children with acute lymphoblastic leukemia (ALL). PCR of full-length IL-7 cDNA enabling the competitive amplification of both variants led to the amplification of diverse unexpected PCR products. The sequence data demonstrated the existence of three additional in-frame splice variants resulting from exon skipping of exon 3 or exon 5 or both in combination with exon 4. We named these IL-7delta3/4, IL-7delta4/5, and IL-7delta3/4/5. Furthermore, three out-of-frame splice variants were identified, IL-7(-56bpExon2), IL-7delta4(-56bpExon2), and IL-7delta3/4/5(-56bpExon2), in which, in addition to the aforementioned exon skipping, 56 bp of the 3' end of exon 2 are omitted. Our results led us to assume that splicing-derived IL-7 isoforms play a potential role in modulating IL-7-mediated biologic effects. Further studies are required to clarify the significance of the diverse IL-7 protein isoforms for the regulation of IL-7 function and the pathogenesis of leukemia. |
| Databáze: | OpenAIRE |
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