Regulation of transcription of the RNA splicing factor hSlu7 by Elk-1 and Sp1 affects alternative splicing
2007; Cold Spring Harbor Laboratory Press; Volume: 13; Issue: 11 Linguagem: Inglês
10.1261/rna.492907
ISSN1469-9001
AutoresMoti Alberstein, Maayan Amit, Keren Vaknin, Amanda O’Donnell, Chen Farhy, Yaniv Lerenthal, Noam Shomron, Ohad Shaham, Andrew D Sharrocks, Ruth Ashery‐Padan, Gil Ast,
Tópico(s)Genomics and Chromatin Dynamics
ResumoAlternative splicing plays a major role in transcriptome diversity and plasticity, but it is largely unknown how tissue-specific and embryogenesis-specific alternative splicing is regulated. The highly conserved splicing factor Slu7 is involved in 3′ splice site selection and also regulates alternative splicing. We show that Slu7 has a unique spatial pattern of expression among human and mouse embryonic and adult tissues. We identified several functional Ets binding sites and GC-boxes in the human Slu7 ( hSlu7 ) promoter region. The Ets and GC-box binding transcription factors, Elk-1 and Sp1 , respectively, exerted opposite effects on hSlu7 transcription: Sp1 protein enhances and Elk-1 protein represses transcription in a dose-dependent manner. Sp1 protein bound to the hSlu7 promoter in vivo, and depletion of Sp1 by RNA interference (RNAi) repressed hSlu7 expression. Elk-1 protein bound to the hSlu7 promoter in vivo, and depletion of Elk-1 by RNAi caused an increase in the endogenous level of hSlu7 mRNA. Further, depletion of either Sp1 or Elk-1 affected alternative splicing. Our results provide indications of a complex transcription regulation mechanism that controls the spatial and temporal expression of Slu7 , presumably allowing regulation of tissue-specific alternative splicing events.
Referência(s)