Functional characterization of five eIF4E isoforms in Caenorhabditis elegans

Functional characterization of five eIF4E isoforms in Caenorhabditis elegans
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DOI:
10.1074/jbc.275.14.10590
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发表时间:
2000-04-07
影响因子:
4.8
通讯作者:
Rhoads, RE
Rhoads, RE
中科院分区:
生物学2区
文献类型:
--
作者:
Keiper, BD;Lamphear, BJ;Rhoads, RE

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eIF4E对mRNA的5'帽结构的识别是大多数mRNA向核糖体募集的关键步骤。在秀丽隐杆线虫中,大约70%的mrna含有不寻常的2,2,7-三甲基鸟苷帽状结构,这是前mrna 5'端反式剪接的结果。在秀丽隐杆线虫中,三种eIF4E亚型(IFE-1, IFE-2和IFE-3)的表征先前有报道。本研究描述了秀丽隐杆线虫中表达的另外两种eIF4E亚型,IFE-4和IFE-5。我们通过RNA干扰分析了每个异构体对生存能力的要求。与哺乳动物eIF4E-1最密切相关的IFE-3仅结合7-甲基鸟苷帽,对生存至关重要。相反,三个密切相关的异构体(IFE-1, IFE-2和IFE-8)结合2,2,7-三甲基鸟苷帽,部分冗余,但至少需要一个功能异构体才能维持生存。IFE-4仅结合7-甲基鸟苷帽,与植物(nCBP)和哺乳动物(4E-HP)中发现的一种不寻常的eIF4E异构体最密切相关,并且在任何IFE敲除组合中都不是生存所必需的。life -2、life -3、life -4和life -5 mrna本身被反接到SL1剪接的先导体上。life -1 mRNA反接到SL2先导上,表明其基因位于操纵子的下游位置。
Recognition of the 5'-cap structure of mRNA by eIF4E is a critical step in the recruitment of most mRNAs to the ribosome. In Caenorhabditis elegans, similar to 70% of mRNAs contain an unusual 2,2,7-trimethylguanosine cap structure as a result of trans-splicing onto the 5' end of the pre-mRNA, The characterization of three eIF4E isoforms in C. elegans (IFE-1, IFE-2, and IFE-3) was reported previously. The present study describes two more eIF4E isoforms expressed in C. elegans, IFE-4 and IFE-5. We analyzed the requirement of each isoform for viability by RNA interference. IFE-3, the most closely related to mammalian eIF4E-1, binds only 7-methylguanosine caps and is essential for viability. In contrast, three closely related isoforms (IFE-1, IFE-2, and IFE-8) bind 2,2,7-trimethylguanosine caps and are partially redundant, but at least one functional isoform is required for viability. IFE-4, which binds only 7-methylguanosine caps, is most closely related to an unusual eIF4E isoform found in plants (nCBP) and mammals (4E-HP) and is not essential for viability in any combination of IFE knockout. ife-2 ife-3 ife-4, and ife-5 mRNAs are themselves trans-spliced to SL1 spliced leaders. ife-1 mRNA is trans-spliced to an SL2 leader, indicating that its gene resides in a downstream position of an operon.