Alternative splicing through intracellular signaling pathways: The emerging importance of diversity and regulation in immune regulation

  • Kamachi Makoto
    First Department of Internal Medicine Unit of Translational Medicine, Graduate School of Biomedical Science, Nagasaki University
  • Eguchi Kastumi
    First Department of Internal Medicine Unit of Translational Medicine, Graduate School of Biomedical Science, Nagasaki University

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  • シグナル伝達経路を介したalternative splicingの誘導―その生物学的意義と制御メカニズム―
  • シグナル デンタツ ケイロ オ カイシタ alternative splicing ノ ユウドウ ソノ セイブツガクテキ イギ ト セイギョ メカニズム

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Abstract

RNA splicing has two different processes: namely, constitutive and alternative splicing. The latter has now emerged as an important mechanism which produces a high degree of protein diversity at a low genetic cost. Importantly, alternative splicing generates functionally distinct products from the same apoptosisrelated genes including Bcl-x, caspase-9, caspase-2, Fas and caspase-8. Furthermore, many genes in the immune system are alternatively spliced including CD45, CD44, CTLA-4 and ICAM-1, thus indicating that alternative splicing plays a critical role in both T-cell homeostasis and the activation-induced cell death (AICD). A critical issue in alternative splicing regulation is the specific recognition of the splice site, which mainly depends on the phosphorylation level of serine/arginine splicing factors (SR proteins). SR proteins are all subjected to phosphorylation and dephosphorylation on Ser residues within their RS domains. Their activities are tightly regulated by reversible phosphorylation. Recently, intensive efforts have been made to obtain new insight into how intracellular signaling regulates RNA splicing. This brief summary outlines both the mechanism and the role of alternative splicing through the intracellular signaling pathways.

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