MODULATION OF EXON SKIPPING AND INCLUSION BY HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN-A1 AND PREMESSENGER RNA SPLICING FACTOR SF2/ASF
MODULATION OF EXON SKIPPING AND INCLUSION BY HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN-A1 AND PREMESSENGER RNA SPLICING FACTOR SF2/ASF
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DOI：
10.1128/mcb.13.5.2993
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发表时间：
1993-05-01
影响因子：
5.3
通讯作者：
KRAINER, AR
中科院分区：
文献类型：
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作者：
MAYEDA, A;HELFMAN, DM;KRAINER, AR
必不可少的剪接因子SF2/ASF和异质核核糖核蛋白A1 （hnRNP A1）在体外调节含有5‘剪接位点的pre- mrna的选择性剪接，这些剪接位点具有竞争共同3’剪接位点的相当强度。利用天然和模型pre- mrna，我们研究了SF2/ASF与hnRNP A1的比例是否也在体外调节其他选择性剪接模式。我们发现过量的SF2/ASF有效地防止了不适当的外显子跳跃，也影响了天然β -原肌球蛋白前mrna中互斥的组织特异性外显子的选择。相反，过量的hnRNP A1不会在天然的组成型或选择性剪接的前mrna中引起不适当的外显子跳变。虽然hnRNP A1可以促进选择性外显子跳跃，但这种作用不是普遍的，而是依赖于，例如，内部选择性外显子的大小和前内含子中聚嘧啶束的强度。在适当的替代外显子中，过量的SF2/ASF促进外显子包含，而过量的hnRNP A1导致外显子跳跃。我们提出，在某些情况下，SF2/ASF与hnRNP A1的比例可能通过外显子包涵或跳过这些蛋白对选择性剪接位点选择的拮抗作用来调节选择性剪接。
The essential splicing factor SF2/ASF and the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) modulate alternative splicing in vitro of pre-mRNAs that contain 5' splice sites of comparable strengths competing for a common 3' splice site. Using natural and model pre-mRNAs, we have examined whether the ratio of SF2/ASF to hnRNP A1 also regulates other modes of alternative splicing in vitro. We found that an excess of SF2/ASF effectively prevents inappropriate exon skipping and also influences the selection of mutually exclusive tissue-specific exons in natural beta-tropomyosin pre-mRNA. In contrast, an excess of hnRNP A1 does not cause inappropriate exon skipping in natural constitutively or alternatively spliced pre-mRNAs. Although hnRNP A1 can promote alternative exon skipping, this effect is not universal and is dependent, e.g., on the size of the internal alternative exon and on the strength of the polypyrimidine tract in the preceding intron. With appropriate alternative exons, an excess of SF2/ASF promotes exon inclusion, whereas an excess of hnRNP A1 causes exon skipping. We propose that in some cases the ratio of SF2/ASF to hnRNP A1 may play a role in regulating alternative splicing by exon inclusion or skipping through the antagonistic effects of these proteins on alternative splice site selection.