Sequence Requirements for Regulated RNA Splicing of the Human Fibroblast Growth Factor Receptor-1 α Exon*
Sequence Requirements for Regulated RNA Splicing of the Human Fibroblast Growth Factor Receptor-1 α Exon*
复制标题
人成纤维细胞生长因子受体 1 α 外显子的受控 RNA 剪接的序列要求*
DOI：
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发表时间：
1997
影响因子：
4.8
通讯作者：
R. Morrison
中科院分区：
文献类型：
--
作者：
G. Cote;E. Huang;W. Jin;R. Morrison
星形胶质细胞从良性到恶性表型的进展伴随着成纤维细胞生长因子受体1（FGFR-1）基因的RNA加工的变化。由于RNA剪接期间的α-外显子跳跃，FGFR-1的高亲和力形式的水平显著升高。在本文中，我们已经能够通过将含有人FGFR-1基因的4-磷酸酶片段（包括α-外显子）的嵌合小基因转染到多种细胞系中来复制这种肿瘤特异性RNA加工途径。在转染的人星形细胞瘤细胞系中，对于来自嵌合小基因和内源性基因表达的RNA转录物，始终观察到α-外显子跳跃。这种外显子跳跃表型依赖于侧翼内含子的大小，因为将内含子减少到小于100350个碱基对的缺失导致α-外显子包含增强。增加的外显子包含不是序列特异性的，因为外显子跳跃可以通过插入非特异性序列来恢复。细胞特异性外显子识别保持在375个核苷酸的序列（含）和α-外显子侧翼，前提是保持内含子大小。这些结果确定了排除星形细胞瘤中FGFR-1 α外显子的最低顺式调控序列要求。
Progression of astrocytes from a benign to a malignant phenotype is accompanied by a change in the RNA processing of the fibroblast growth factor receptor 1 (FGFR-1) gene. The level of a high affinity form of the FGFR-1 is dramatically elevated as a result of α-exon skipping during RNA splicing. In this paper we have been able to duplicate this tumor-specific RNA processing pathway by transfection of a chimeric minigene containing a 4-kilobase fragment of the human FGFR-1 gene (including the α-exon) into a variety of cell lines. In a transfected human astrocytoma cell line, α-exon skipping was consistently observed for RNA transcripts derived from both the chimeric minigene and endogenous gene expression. This exon skipping phenotype was dependent on the size of the flanking intron as deletions which reduced the introns to less than ∼350 base pairs resulted in enhanced α-exon inclusion. Increased exon inclusion was not sequence-specific as exon skipping could be restored with insertion of nonspecific sequence. Cell-specific exon recognition was maintained with a 375-nucleotide sequence inclusive and flanking the α-exon, provided that intron size was maintained. These results identify the minimal cis-regulatory sequence requirements for exclusion of FGFR-1 α-exon in astrocytomas.
影响因子：
--
作者：
Daniel E. Johnson;L. Williams
通讯作者：
Daniel E. Johnson;L. Williams
影响因子：
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作者：
H. Lou;G. Cote;R. Gagel
通讯作者：
H. Lou;G. Cote;R. Gagel
影响因子：
3.5
作者：
DONISKELLER, H;DOU, SS;WELLS, SA
通讯作者：
WELLS, SA