ID 111998
著者
Kanazawa, Keisuke Tokushima University
Kimura, Maria Tokushima University
Ike, Hironobu Tokushima University
Shinomiya, Makiko Tokushima University
Tanaka, Shouko Tokushima University
キーワード
Exon skipping
Galactosialidosis
RNA splicing
Splice defect
資料タイプ
学術雑誌論文
抄録
Cathepsin A (CTSA) is a multifunctional lysosomal enzyme, and its hereditary defect causes an autosomal recessive disorder called galactosialidosis. In a certain number of galactosialidosis patients, a base substitution from adenine to guanine is observed at the +3 position of the 7th intron (IVS7 +3a>g) of the CTSA gene. With this mutation, a splicing error occurs; and consequently mRNA lacking the 7th exon is produced. This skipping of exon 7 causes a frame shift of the transcripts, resulting in a non-functional CTSA protein and hence galactosialidosis. This mutation seems to make the interaction between the 5’-splice site of intron 7 of pre-mRNA and U1 small nuclear RNA (U1 snRNA) much weaker. In the present study, to produce properly spliced mRNA from the CTSA gene harboring this IVS7 +3a>g mutation, we examined the possible usefulness of modified U1 snRNA that could interact with the mutated 5’-splice site. Toward this goal, we first prepared a model system using a mutant CTSA mini gene plasmid for delivery into HeLa cells. Then, we examined the effectiveness of modified U1 snRNA on the formation of properly spliced mRNA from this mutant CTSA mini gene. As a result, we succeeded in obtaining improved formation of properly spliced CTSA mRNA. Our results suggest the usefulness of modified U1 snRNA for rescue from exon 7 skipping caused by the IVS7 +3a>g mutation of the CTSA gene.
掲載誌名
Gene
ISSN
03781119
cat書誌ID
AA00654385
AA11529840
出版者
Elsevier
677
開始ページ
41
終了ページ
48
発行日
2018-07-24
備考
論文本文は2019-07-24公開予定。
権利情報
© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
EDB ID
出版社版DOI
出版社版URL
言語
eng
著者版フラグ
その他
部局
薬学系
先端酵素学研究所