Uncoupling of Expression of an Intronic MicroRNA and Its Myosin Host Gene by Exon Skipping

Uncoupling of Expression of an Intronic MicroRNA and Its Myosin Host Gene by Exon Skipping
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DOI:
10.1128/mcb.01370-09
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发表时间:
2010-04-15
影响因子:
5.3
通讯作者:
Leinwand, Leslie A.
Leinwand, Leslie A.
中科院分区:
生物学2区
文献类型:
--
作者:
Bell, Matthew L.;Buvoli, Massimo;Leinwand, Leslie A.

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在横纹肌和脑中表达的古老MYH 7 b基因编码肌节肌球蛋白和内含子microRNA miR-499。我们发现外显子的跳跃在转录本中引入了一个提前终止密码子,该密码子下调MYH 7 b蛋白的产生而不影响microRNA的表达。在其他基因中,内源性miR-499靶向转录因子Sox 6的3'非翻译区,其进而充当MYH 7 b转录活性的阻遏物。因此,当不需要MYH 7 b和miR-499的共表达时,协同转录和选择性剪接解除了它们的表达水平。
The ancient MYH7b gene, expressed in striated muscle and brain, encodes a sarcomeric myosin and the intronic microRNA miR-499. We find that skipping of an exon introduces a premature termination codon in the transcript that downregulates MYH7b protein production without affecting microRNA expression. Among other genes, endogenous miR-499 targets the 3' untranslated region of the transcription factor Sox6, which in turn acts as a repressor of MYH7b transcriptional activity. Thus, concerted transcription and alternative splicing uncouple the level of expression of MYH7b and miR-499 when their coexpression is not required.