RNA SECONDARY STRUCTURE REPRESSION OF A MUSCLE-SPECIFIC EXON IN HELA-CELL NUCLEAR EXTRACTS
RNA SECONDARY STRUCTURE REPRESSION OF A MUSCLE-SPECIFIC EXON IN HELA-CELL NUCLEAR EXTRACTS
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DOI：
10.1126/science.2063195
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发表时间：
1991-06-28
期刊：
影响因子：
56.9
通讯作者：
MARIE, J
中科院分区：
文献类型：
--
作者：
DORVAL, BC;CARAFA, YD;MARIE, J
鸡β -原肌球蛋白前信使RNA （pre-mRNA）以组织特异性方式剪接，产生编码该蛋白不同亚型的信使RNA （mRNA）。外显子6A和6B以互斥方式拼接；外显子6B包含在骨骼肌中，而外显子6A在所有其他组织中都是首选的。外显子6B上游的内含子远端部分与外显子6B下游的部分内含子以及外显子6B中的序列形成稳定的双链区域。这种结构抑制HeLa细胞提取物外显子6B到外显子7的剪接。剪接的抑制发生在这种结构的破坏上，而当这种结构重新形成时，即使这种结构是在两个不同的RNA分子之间形成的，剪接也会受到抑制。抑制导致剪接体形成的抑制。破坏两个双链区域中的任何一个都可能导致抑制，而通过抑制突变重新形成螺旋则会重新建立抑制。这些结果支持一个简单的模型，组织特异性剪接在这一区域的前mrna。
The chicken beta-tropomyosin pre-messenger RNA (pre-mRNA) is spliced in a tissue-specific manner to yield messenger RNA's (mRNA's) coding for different isoforms of this protein. Exons 6A and 6B are spliced in a mutually exclusive manner; exon 6B was included in skeletal muscle, whereas exon 6A was preferred in all other tissues. The distal portion of the intron upstream of exon 6B was shown to form stable double-stranded regions with part of the intron downstream of exon 6B and with sequences in exon 6B. This structure repressed splicing of exon 6B to exon 7 in a HeLa cell extract. Derepression of splicing occurred on disruption of this structure and repression followed when the structure was re-formed, even if the structure was formed between two different RNA molecules. Repression leads to inhibition of formation of spliceosomes. Disrupting either of the two double-stranded regions could lead to derepression, whereas re-forming the helices by suppressor mutations reestablished repression. These results support a simple model of tissue-specific splicing in this region of the pre-mRNA.