期刊
NUCLEIC ACIDS RESEARCH
卷 39, 期 10, 页码 4300-4314出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq1267
关键词
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资金
- Cell Dynamics Research Center [2010-0001621]
- National Research Foundation of Korea/Ministry of Education, Science and 65 Technology [2008-0060838]
- Korean government, Korea Research Foundation [KRF-2008-314-C00265]
- BioImaging Research Center at GIST
- Korean government, Korea Research 70 Foundation [KRF-2008-314-C00265]
- National Research Foundation of Korea [2008-314-C00265, 2008-0060838] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Grants-in-Aid for Scientific Research [23310135] Funding Source: KAKEN
Nuclear speckles are known to be the storage sites of mRNA splicing regulators. We report here the identification and characterization of a novel speckle protein, referred to as NSrp70, based on its subcellular localization and apparent molecular weight. This protein was first identified as CCDC55 by the National Institutes of Health Mammalian Gene Collection, although its function has not been assigned. NSrp70 was colocalized and physically interacted with SC35 and ASF/SF2 in speckles. NSrp70 has a putative RNA recognition motif, the RS-like region, and two coiled-coil domains, suggesting a role in RNA processing. Accordingly, using CD44, Tra2 beta 1 and Fas constructs as splicing reporter minigenes, we found that NSrp70 modulated alternative splice site selection in vivo. The C-terminal 10 amino acids (531-540), including (RD537)-R-536, were identified as a novel nuclear localization signal, and the region spanning 290-471 amino acids was critical for speckle localization and binding to SC35 and ASF/SF2. The N-terminal region (107-161) was essential for the pre-mRNA splicing activity. Finally, we found that knockout of NSrp70 gene in mice led to a lack of progeny, including fetal embryos. Collectively, we demonstrate that NSrp70 is a novel splicing regulator and essentially required early stage of embryonic development.
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