Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5'-terminal regions of cap0-, cap1- and 5'ppp- mRNAs.
Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5'-terminal regions of cap0-, cap1- and 5'ppp- mRNAs.
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DOI：
10.1093/nar/gkt1321
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发表时间：
2014-03
影响因子：
14.9
通讯作者：
Pestova TV
中科院分区：
文献类型：
--
作者：
Kumar P;Sweeney TR;Skabkin MA;Skabkina OV;Hellen CU;Pestova TV
细胞mRNA的核糖体募集依赖于eIF4F与mRNA的5 ‘端’帽'的结合。最小的“cap0”由n7 -甲基鸟苷组成，通过5 ‘ -5 ’三磷酸（ppp）桥连接到第一个核苷酸。随后两个核糖的2 ‘ - o -甲基化进一步修饰Cap0，生成’ cap1 ‘ （m7GpppNmN）和’ cap2 ' （m7GpppNmNm）。然而，一些病毒rna缺乏2 ‘ - o -甲基化，而另一些病毒rna在其5 ’端仅含有ppp-。干扰素诱导的四肽重复蛋白（IFITs）是先天免疫的高表达效应物，其抑制病毒复制的机制尚不完全清楚。在这里，我们研究了IFIT家族成员与cap1-， cap0-和5'ppp - mrna相互作用并抑制其翻译的能力。IFIT1和IFIT1B对cap0- mrna的cap-近端区域表现出非常高的亲和力（K1/2,app ~ 9 ~ 23 nM）。2 ' - o -甲基化消除了IFIT1/mRNA的相互作用，而IFIT1B保留了结合cap1-mRNA的能力，尽管亲和力降低（K1/2,app ~ 450 nM）。5 ‘ pp- mrna的5 ’末端区域被IFIT5识别（K1/2,app ~ 400 nM）。单个IFITs抑制特定mRNA启动的活性取决于它们与其5 ‘端区相互作用的能力：IFIT1和IFIT1B有效地胜过eIF4F，并消除了对cap0-mRNA的启动，而IFIT1B和IFIT5对cap1-和5 ’ ppp- mRNA的抑制作用较弱，需要更高的蛋白质浓度。
Ribosomal recruitment of cellular mRNAs depends on binding of eIF4F to the mRNA’s 5′-terminal ‘cap’. The minimal ‘cap0’ consists of N7-methylguanosine linked to the first nucleotide via a 5′-5′ triphosphate (ppp) bridge. Cap0 is further modified by 2′-O-methylation of the next two riboses, yielding ‘cap1’ (m7GpppNmN) and ‘cap2’ (m7GpppNmNm). However, some viral RNAs lack 2′-O-methylation, whereas others contain only ppp- at their 5′-end. Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed effectors of innate immunity that inhibit viral replication by incompletely understood mechanisms. Here, we investigated the ability of IFIT family members to interact with cap1-, cap0- and 5′ppp- mRNAs and inhibit their translation. IFIT1 and IFIT1B showed very high affinity to cap-proximal regions of cap0-mRNAs (K1/2,app ∼9 to 23 nM). The 2′-O-methylation abrogated IFIT1/mRNA interaction, whereas IFIT1B retained the ability to bind cap1-mRNA, albeit with reduced affinity (K1/2,app ∼450 nM). The 5′-terminal regions of 5′ppp-mRNAs were recognized by IFIT5 (K1/2,app ∼400 nM). The activity of individual IFITs in inhibiting initiation on a specific mRNA was determined by their ability to interact with its 5′-terminal region: IFIT1 and IFIT1B efficiently outcompeted eIF4F and abrogated initiation on cap0-mRNAs, whereas inhibition on cap1- and 5′ppp- mRNAs by IFIT1B and IFIT5 was weaker and required higher protein concentrations.
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影响因子：
64.8
作者：
Abbas YM;Pichlmair A;Górna MW;Superti-Furga G;Nagar B
通讯作者：
Nagar B
影响因子：
5.4
作者：
Berchtold, Susanne;Lampe, Johanna;Lauer, Ulrich M.
通讯作者：
Lauer, Ulrich M.
影响因子：
16
作者：
Gu, MG;Fabrega, C;Lima, CD
通讯作者：
Lima, CD
影响因子：
5.6
作者：
Brown, Christopher J.;McNae, Iain;Walkinshaw, Malcolm D.
通讯作者：
Walkinshaw, Malcolm D.
影响因子：
10.5
作者：
Hogg, J. Robert;Collins, Kathleen
通讯作者：
Collins, Kathleen