SKIP modifies gene expression by affecting both transcription and splicing.
SKIP has been described as a transcriptional coregulator as well as a spliceosome component, but the relationship between these functions is not clear. We found that SKIP activated reporter gene expression from the basal promoters of viral origin. SKIP exhibited more prominent effect on the promoters with stronger activities, in an experiment employing a series of reporter constructs carrying different numbers of GC boxes. We also found that SKIP suppressed aberrant splicing at a cryptic splice donor site in the luciferase reporter gene. In addition, SKIP suppressed splicing of an extra intron created by a beta-thalassemia mutation in the human beta-globin gene. In the transfection experiment, an intronless reporter exhibited a higher level of expression, but was less significantly activated by SKIP, than the intron-containing reporter. These results indicate that SKIP affects gene expression by both transcriptional activation and regulation of pre-mRNA splicing.
Nagai
Keisuke
K
Department of Life Science, Graduate School of Science, Himeji Institute of Technology, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan.
Yamaguchi
Tomohiro
T
Takami
Tomonori
T
Kawasumi
Aiko
A
Aizawa
Masakazu
M
Masuda
Nobuyuki
N
Shimizu
Makoto
M
Tominaga
Sachiko
S
Ito
Takashi
T
Tsukamoto
Toshiro
T
Osumi
Takashi
T
D000818:Animals; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D009687:Nuclear Proteins / Q000502:physiology*; D056918:Nuclear Receptor Coactivators; D011401:Promoter Regions, Genetic; D012322:RNA Precursors / Q000378:metabolism; D012326:RNA Splicing; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D015533:Transcriptional Activation
D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D012322:RNA Precursors; C111791:SNW1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors