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ID 109685
Title Alternative
酸化ストレスにより誘導されるtruncated serine/arginine –rich splicing factor 3はヒト大腸癌細胞のインターロイキン8の産生を調節する
Truncated SRSF3 regulates IL-8 production
Author
Kano, Shizuka The University of Tokushima
Kurebe, Hiroyuki The University of Tokushima
Nishiyama, Chihiro The University of Tokushima
Kita, Kentaro The University of Tokushima
Akaike, Yoko The University of Tokushima
Kajita, Keisuke The University of Tokushima
Kurokawa, Ken The University of Tokushima
Masuda, Kiyoshi The University of Tokushima KAKEN Search Researchers
Tanahashi, Toshihito The University of Tokushima
Keywords
SRSF3遺伝子
酸化ストレス
選択的スプライシング
ナンセンス変異依存mRNA分解機構
インターロイキン8
SRSF3 gene
oxidative stress
alternative splicing
nonsense-mediated mRNA decay
IL-8
Content Type
Thesis or Dissertation
Description
Serine/arginine-rich splicing factor 3 (SRSF3) is a member of the SR protein family and plays wide-ranging roles in gene expression. The human SRSF3 gene generates two alternative splice transcripts, a major mRNA isoform (SRSF3-FL) encoding functional full-length protein and a premature termination codon (PTC)-containing isoform (SRSF3-PTC). The latter is degraded through nonsense-mediated mRNA decay (NMD). Treatment of a human colon cancer cell line (HCT116) with 100 μM sodium arsenite increased SRSF3-PTC mRNA levels without changing SRSF3-FL mRNA levels. A chemiluminescence-based NMD reporter assay system demonstrated that arsenite treatment inhibited NMD activity and increased SRSF3-PTC mRNA levels in the cytoplasm, facilitating translation of a truncated SRSF3 protein (SRSF3-TR) from SRSF3-PTC mRNA. SRSF3-TR lacked two-thirds of Arg/Ser-rich (RS) domain whose phosphorylation state is known to be crucial for subcellular distribution. SRSF3-FL was localized in the nucleus, while overexpressed SRSF3-TR was diffusely distributed in the cytoplasm and the nucleus. A part of SRSF3-TR was also associated with stress granules in the cytoplasm. Interestingly, treatment of HCT116 cells with a small interference RNA specifically targeting SRSF3-PTC mRNA significantly attenuated arsenite-stimulated induction of c-JUN protein, its binding activity to the AP-1 binding site (-126 to 120 bp) in the interleukin (IL)-8 gene promoter, and AP-1 promoter activity, resulting in significant reduction of arsenite-stimulated IL-8 production. Our results suggest that SRSF3-TR may function as a positive regulator of oxidative stress-initiated inflammatory responses in colon cancer cells.
Journal Title
American Journal of Physiology. Cell Physiology
ISSN
03636143
15221563
NCID
AA00521122
Publisher
the American Physiological Society
Volume
306
Issue
3
Start Page
C250
End Page
C262
Published Date
2014-02-01
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201606061012.pdf
論文本文 : k2903_fulltext.pdf
本論文は,著者Shizuka Kanoの学位論文として提出され,学位審査・授与の対象となっている。
著者の申請により要約(2016-06-07公開)に替えて論文全文を公開(2019-12-19)
Rights
© 2014 the American Physiological Society
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2903号
Diploma Number
甲医第1277号
Granted Date
2016-03-23
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences