Stress alters the subcellular distribution of hSlu7 and thus modulates alternative splicing
Autor: | Gil Ast, Mika Reznik, Noam Shomron, Moti Alberstein |
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Rok vydání: | 2005 |
Předmět: |
RNA Splicing Factors
Cytoplasm Spliceosome Time Factors Cell Survival Ultraviolet Rays Recombinant Fusion Proteins Blotting Western Molecular Sequence Data Active Transport Cell Nucleus Biology Cell Line Exon Splicing factor Cell Line Tumor Sequence Homology Nucleic Acid Image Processing Computer-Assisted Humans RNA Messenger Phosphorylation Glutathione Transferase Cell Nucleus Base Sequence Models Genetic Reverse Transcriptase Polymerase Chain Reaction Alternative splicing JNK Mitogen-Activated Protein Kinases Temperature Intron Exons Cell Biology Ribonucleoproteins Small Nuclear Molecular biology Introns Cell biology Alternative Splicing Microscopy Fluorescence RNA splicing Spliceosomes RNA RNA Interference HeLa Cells Minigene |
Zdroj: | Journal of Cell Science. 118:1151-1159 |
ISSN: | 1477-9137 0021-9533 |
DOI: | 10.1242/jcs.01720 |
Popis: | During pre-mRNA splicing, introns are removed and exons are ligated to form an mRNA. Exon choice is determined by different nuclear protein concentrations varying among tissues and cell types or by developmental stage. These can be altered by different cellular circumstances such as physiological stimuli, environmental effects and phosphorylation state. The splicing factor hSlu7 plays an important role in 3′ splice site selection during the second step of splicing in vitro and has been suggested to affect alternative splicing in vivo. Our results indicate that an ultraviolet-C (UV-C) stress stimulus triggers changes in the alternative splicing patterns of cellular genes by decreasing the nuclear concentration of hSlu7 through the modulation of its nucleus-to-cytoplasm transport. This shift is mostly dependent on the Jun N-terminal kinase (JNK) cascade. Although we found by RNAi knockdown that hSlu7 is not essential for cell viability, its nuclear concentration effects exon choice and inclusion:skipping ratio of alternative splicing. A possible spatial and temporal regulatory mechanism by which hSlu7 protein levels are regulated within the nucleus is suggested, thus implying a broad effect of hSlu7 on alternative splicing. |
Databáze: | OpenAIRE |
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