Exploring Internal Ribosome Entry Sites as Therapeutic Targets.
Exploring Internal Ribosome Entry Sites as Therapeutic Targets.
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DOI：
10.3389/fonc.2015.00233
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发表时间：
2015
影响因子：
4.7
通讯作者：
Hatzoglou M
中科院分区：
文献类型：
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作者：
Komar AA;Hatzoglou M
真核生物mRNA翻译的起始可以通过几种不同的途径进行，每种途径都需要不同的因子子集，并依赖于mRNA和核糖体之间不同的特异性相互作用。两种模式占主导地位：（i）所谓的帽依赖性起始，其需要所有典型的起始因子，并且负责真核细胞中约95-97%的所有起始事件;和（ii）帽非依赖性内部起始，其需要减少的起始因子子集，并且占剩余起始事件的高达5%。内部起始依赖于一些病毒和细胞mRNA的5′ UTR中存在所谓的内部核糖体进入位点（IRES）元件。这些元件（通常具有复杂的二级和三级结构）促进mRNA与40 S核糖体的有效相互作用，并允许内部核糖体进入。特定mRNA翻译的内部启动可能有助于严重疾病和病理状态的发展，如丙型肝炎和癌症。因此，这种细胞机制代表了药理学调节的有吸引力的靶标。本综述的目的是提供深入了解目前用于靶向病毒和细胞IRES的策略，并讨论废除/调节IRES介导的翻译的生理后果（和潜在的治疗意义）。
Initiation of eukaryotic mRNA translation may proceed via several different routes, each requiring a different subset of factors and relying on different and specific interactions between the mRNA and the ribosome. Two modes predominate: (i) so-called cap-dependent initiation, which requires all canonical initiation factors and is responsible for about 95–97% of all initiation events in eukaryotic cells; and (ii) cap-independent internal initiation, which requires a reduced subset of initiation factors and accounts for up to 5% of the remaining initiation events. Internal initiation relies on the presence of so-called internal ribosome entry site (IRES) elements in the 5′ UTRs of some viral and cellular mRNAs. These elements (often possessing complex secondary and tertiary structures) promote efficient interaction of the mRNA with the 40S ribosome and allow for internal ribosome entry. Internal initiation of translation of specific mRNAs may contribute to development of severe disease and pathological states, such as hepatitis C and cancer. Therefore, this cellular mechanism represents an attractive target for pharmacological modulation. The purpose of this review is to provide insight into current strategies used to target viral and cellular IRESs and discuss the physiological consequences (and potential therapeutic implications) of abrogation/modulation of IRES-mediated translation.
影响因子：
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作者：
Berry KE;Peng B;Koditek D;Beeman D;Pagratis N;Perry JK;Parrish J;Zhong W;Doudna JA;Shih IH
通讯作者：
Shih IH