Exon junction complex subunits are required to splice Drosophila MAP kinase, a large heterochromatic gene.

Exon junction complex subunits are required to splice Drosophila MAP kinase, a large heterochromatic gene.
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DOI:
10.1016/j.cell.2010.09.036
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发表时间:
2010-10-15
期刊:
影响因子:
64.5
通讯作者:
Treisman JE
Treisman JE
中科院分区:
生物学1区
文献类型:
--
作者:
Roignant JY;Treisman JE

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外显子连接复合物 (EJC) 组装在外显子-外显子连接上游的剪接 mRNA 上,可以调节其随后的翻译、定位或降解。我们在果蝇 mago nashi (mago) 中分离出了突变,该突变编码核心 EJC 亚基,基于其对光感受器分化的意外特异性影响。由于 MAPK mRNA 水平大幅降低,Mago 的缺失会阻止表皮生长因子受体信号传导。 MAPK 表达还需要 EJC 亚基 Y14 和 eIF4AIII 以及 EJC 相关剪接因子。 Mago 耗竭不会影响 MAPK mRNA 的转录或稳定性,但会改变其剪接模式。仅当模板包含内含子时,外源启动子的 MAPK 表达才需要 Mago。 MAPK是眼睛发育中mago的主要功能靶点;在培养细胞中,Mago 敲低会不成比例地影响位于异染色质中的其他大基因。这些数据支持 EJC 组件在剪接特定内含子子集中的核作用。
The exon junction complex (EJC) is assembled on spliced mRNAs upstream of exon-exon junctions, and can regulate their subsequent translation, localization, or degradation. We isolated mutations in Drosophila mago nashi (mago), which encodes a core EJC subunit, based on their unexpectedly specific effects on photoreceptor differentiation. Loss of Mago prevents Epidermal growth factor receptor signaling, due to a large reduction in MAPK mRNA levels. MAPK expression also requires the EJC subunits Y14 and eIF4AIII, and EJC-associated splicing factors. Mago depletion does not affect the transcription or stability of MAPK mRNA, but alters its splicing pattern. MAPK expression from an exogenous promoter requires Mago only when the template includes introns. MAPK is the primary functional target of mago in eye development; in cultured cells, Mago knockdown disproportionately affects other large genes located in heterochromatin. These data support a nuclear role for EJC components in splicing a specific subset of introns.
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