DHX29 and eIF3 cooperate in ribosomal scanning on structured mRNAs during translation initiation.

DHX29 and eIF3 cooperate in ribosomal scanning on structured mRNAs during translation initiation.
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DOI:
10.1261/rna.057851.116
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发表时间:
2016-12
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
Pisarev AV
Pisarev AV
中科院分区:
其他
文献类型:
--
作者:
Pisareva VP;Pisarev AV

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真核生物翻译起始是一个涉及许多组分的复杂过程。eIF3是多种起始因子的支架,在起始过程中发挥多种作用,而DHX29解旋酶促进结构化mRNA上48S起始复合物的形成。由于DHX29不是一种持续性解旋酶,其活性的潜在机制尚不清楚。在此,我们表明DHX29与eIF3建立了许多接触点。特别是,DHX29独特的N末端与eIF3b的RNA识别基序以及eIF3的eIF3a亚基的C末端相关联,并且任何一种接触的破坏都会损害DHX29的活性。反过来,DHX29在48S起始复合物中与mRNA的接触点较弱,并且mRNA所经过的路径保持不变。这些结果排除了该蛋白在解旋中的直接作用。因此,DHX29和eIF3在结构化mRNA的扫描过程中相互协作。我们的发现支持了先前关于eIF3在扫描过程中作用的遗传学数据。
Eukaryotic translation initiation is a complex process involving many components. eIF3 is a scaffold for multiple initiation factors and plays multiple roles in initiation, and DHX29 helicase enhances the formation of the 48S initiation complex on structured mRNAs. Because DHX29 is not a processive helicase, the mechanism underlying its activity is unclear. Here, we show that DHX29 establishes many points of contact with eIF3. In particular, the unique N terminus of DHX29 associates with the RNA recognition motif of eIF3b and the C terminus of the eIF3a subunits of eIF3, and the disruption of either contact impairs DHX29 activity. In turn, DHX29 has weak points of contact with mRNA in the 48S initiation complex, and the pathway taken by mRNA remains unchanged. These results exclude the direct role for this protein in unwinding. Thus, DHX29 and eIF3 cooperate in scanning on structured mRNAs. Our findings support previous genetic data on the role of eIF3 during scanning.
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