Increased Serine-Arginine (SR) Protein Phosphorylation Changes Pre-mRNA Splicing in Hypoxia.
作者： Egle Jakubauskiene , Laurynas Vilys , Yuichi Makino , Lorenz Poellinger , Arvydas Kanopka
关键词:
摘要: The removal of introns from mRNA precursors (pre-mRNAs) is an essential step in eukaryotic gene expression. splicing machinery heavily contributes to biological complexity and especially the ability cells adapt altered cellular conditions. Inhibitory PAS domain protein (IPAS), a dominant negative regulator hypoxia-inducible expression, generated hypoxia inducible transcription factor-3α (HIF-3α) pre-mRNA by alternative mechanism. Inactivation IPAS transcript mice leads neo-vascularization cornea, suggesting that important anti-angiogenesis this tissue. For first time we demonstrate serine-arginine (SR) proteins are involved oxygen tension-dependent changes splicing. SR isolated hypoxic differentially interact with RNA (compared cultured under normoxic conditions). They possess differential activate hypoxia-dependent splice sites, they more phosphorylated than those HeLa cells. We also show expression kinases (CLK1, SRPK1, SRPK2) elevated at levels. Increased CLK1 kinase regulated HIFs. Reduction levels reduces full-length carbonic anhydrase IX (CAIX) CAIX formation cysteine-rich angiogenic inducer 61 (Cyr61) isoform profiles.
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