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1型人类免疫缺陷病毒中参与核糖体移码的茎环结构形成的直接结构证据。

Direct structural evidence for formation of a stem-loop structure involved in ribosomal frameshifting in human immunodeficiency virus type 1.

作者信息

Kang H

机构信息

Kumho Life and Environmental Science Laboratory, Korea Kumho Petrochemical Co. Ltd., Kwangju, South Korea.

出版信息

Biochim Biophys Acta. 1998 Apr 1;1397(1):73-8. doi: 10.1016/s0167-4781(98)00004-9.

DOI:10.1016/s0167-4781(98)00004-9
PMID:9545540
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7148724/
Abstract

Programmed ribosomal frameshifting in viral messenger RNA occurs in response to neighboring sequence elements consisting of: a frameshift site, a spacer, and a downstream enhancer sequence. In human immunodeficiency virus type 1 (HIV-1) mRNA, this sequence element has a potential to form either a stem-loop or a pseudoknot structure. Based on many mutational studies, the stem-loop structure has been proposed for the downstream enhancer region of the HIV-1 mRNA. This stimulatory stem-loop structure is separated from the shift site by a spacer of seven nucleotides. In contrast, a recent report has proposed an alternative model in which the bases in the spacer sequence form a pseudoknot structure as the downstream enhancer sequence [Du et al., Biochemistry 35 (1996) 4187-4198.]. Using UV melting and enzymatic mapping analyses, we have investigated the conformation of the sequence region involved in ribosomal frameshifting in HIV-1. Our S1, V1, and T1 endonuclease mappings, together with UV melting analysis, clearly indicate that this sequence element of the HIV-1 mRNA frameshift site forms a stem-loop structure, not a pseudoknot structure. This finding further supports the stem-loop structure proposed by many mutational studies for the downstream enhancer sequence of the HIV-1 mRNA.

摘要

病毒信使核糖核酸中的程序性核糖体移码是对由以下部分组成的相邻序列元件作出的反应

一个移码位点、一个间隔区和一个下游增强子序列。在1型人类免疫缺陷病毒(HIV-1)信使核糖核酸中,该序列元件有可能形成茎环结构或假结结构。基于许多突变研究,有人提出HIV-1信使核糖核酸下游增强子区域存在茎环结构。这种刺激性茎环结构与移码位点之间由七个核苷酸的间隔区分开。相比之下,最近有一份报告提出了另一种模型,即间隔区序列中的碱基与下游增强子序列一起形成假结结构[Du等人,《生物化学》35(1996)4187 - 4198]。通过紫外熔解和酶切图谱分析,我们研究了HIV-1中参与核糖体移码的序列区域的构象。我们的S1、V1和T1核酸内切酶图谱分析以及紫外熔解分析清楚地表明,HIV-1信使核糖核酸移码位点的这个序列元件形成的是茎环结构,而非假结结构。这一发现进一步支持了许多突变研究提出的关于HIV-1信使核糖核酸下游增强子序列的茎环结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/7148724/68fa5b0e8d96/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/7148724/91ef15dcfb2c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/7148724/2f9d1631fed4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/7148724/a5de88a17c7f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/7148724/68fa5b0e8d96/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/7148724/91ef15dcfb2c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/7148724/2f9d1631fed4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/7148724/a5de88a17c7f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/7148724/68fa5b0e8d96/gr4.jpg

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本文引用的文献

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An NMR and mutational study of the pseudoknot within the gene 32 mRNA of bacteriophage T2: insights into a family of structurally related RNA pseudoknots.噬菌体T2基因32 mRNA内假结的核磁共振与突变研究:对一类结构相关RNA假结的深入了解
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The human immunodeficiency virus type 1 ribosomal frameshifting site is an invariant sequence determinant and an important target for antiviral therapy.人类免疫缺陷病毒1型核糖体移码位点是一个不变的序列决定因素,也是抗病毒治疗的重要靶点。
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