M Komatsu1, E Kominami, K Arahata, T Tsukahara. 1. Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Ogawahigashi 4-1-1, Kodaira, Tokyo 187-8502, Japan; Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan.
Abstract
BACKGROUND: In neurones, alternative splicing regulates the functions of many gene products. However, the molecular basis of neural-specific splicing, and how splicing regulation is modulated in different neurones remains to be determined. RESULTS: We cloned two new SR proteins, Neural-salient SR proteins (NSSR) 1 and 2, which are present at higher levels in brain and testis. During the differentiation, NSSR 1 is detected only in the neuronal stage. Both the purified recombinant NSSR 1 and 2 proteins enhance the in vitro splicing activity of nuclear extract. Moreover, recombinant NSSR 1 protein enhances the assembly of ribonucleoprotein complexes with S100 fraction. Over-expression of NSSR 2 prevents the inclusion of either the Flip or Flop exons in the splicing of the GluR-B gene, resulting in an increase in the abnormal exon-skipping product. In contrast, transient transfection with NSSR 1 promotes the inclusion of the Flip exon so that the abnormal product is spliced to the mature spliced form. This suppression of exon skipping by NSSR 1 is observed even with co-transfection of NSSR 2. CONCLUSIONS: NSSR 1 and 2 were cloned from mouse cDNA libraries. Results indicate that NSSR 1 may play a crucial role in the regulation of alternative splicing in neurones.
BACKGROUND: In neurones, alternative splicing regulates the functions of many gene products. However, the molecular basis of neural-specific splicing, and how splicing regulation is modulated in different neurones remains to be determined. RESULTS: We cloned two new SR proteins, Neural-salient SR proteins (NSSR) 1 and 2, which are present at higher levels in brain and testis. During the differentiation, NSSR 1 is detected only in the neuronal stage. Both the purified recombinant NSSR 1 and 2 proteins enhance the in vitro splicing activity of nuclear extract. Moreover, recombinant NSSR 1 protein enhances the assembly of ribonucleoprotein complexes with S100 fraction. Over-expression of NSSR 2 prevents the inclusion of either the Flip or Flop exons in the splicing of the GluR-B gene, resulting in an increase in the abnormal exon-skipping product. In contrast, transient transfection with NSSR 1 promotes the inclusion of the Flip exon so that the abnormal product is spliced to the mature spliced form. This suppression of exon skipping by NSSR 1 is observed even with co-transfection of NSSR 2. CONCLUSIONS:NSSR 1 and 2 were cloned from mouse cDNA libraries. Results indicate that NSSR 1 may play a crucial role in the regulation of alternative splicing in neurones.
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