Cleavage of oligoribonucleotides by a ribozyme derived from the hepatitis delta virus RNA sequence.
Cleavage of oligoribonucleotides by a ribozyme derived from the hepatitis delta virus RNA sequence.
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源自丁型肝炎病毒 RNA 序列的核酶对寡核糖核苷酸的切割。
DOI：
10.1021/bi00116a004
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发表时间：
1992
期刊：
影响因子：
2.9
通讯作者：
Been,MD
中科院分区：
文献类型：
--
作者：
Perrotta,AT;Been,MD
杜克大学医学中心生物化学系，达勒姆，北卡罗来纳州27710接收于1991年9月25日;修订于1991年11月5日摘要：对来自5型肝炎病毒的自切割RNA序列进行修饰，以产生能够在分子间（反式）反应中催化RNA切割的核酶。5-衍生的核酶在特定位点切割底物RNA，并且序列特异性可以随着核酶与底物碱基配对区域的突变而改变。鉴定了长度为约8个核苷酸的底物靶大小。在切割位点5 ′端含有一个核糖核苷酸的八核苷酸是切割的底物，只有在该位置有鸟嘌呤碱基时切割活性才显著降低。切割位点5 '端的脱氧核糖阻断了反应。这些数据与所提出的8型肝炎病毒核酶自切割形式的二级结构一致，其中双链体与切割位点的3 '端序列形成，并且它们支持一种提出的机制，其中裂解涉及通过相邻的2 ′-羟基攻击裂解位点处的磷。在某些同时感染B型肝炎的患者中发现的单链RNA病毒（Taylor，1990）。存在于基因组RNA和互补反基因组RNA两者中的自切割序列可以在病毒RNA的滚环复制期间起作用以加工RNA（Kuo等人，1988; Sharmeen等人，1988; Wu等人，1989年）。因此，HDV RNA可能是第一个明确的自催化RNA（核酶）的例子，它以其天然形式在人类细胞中发挥作用。随着HDV RNA中自切割序列的鉴定（Kuo等人，1988; Sharmeen等人，1988; Wu等人，1989），有人提出HDV自切割结构必须代表与其他自切割RNA不同的结构基序（Hutchins et al.，
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710 Received September 25, 1991; Revised Manuscript Received November 5, 1991 abstract: A self-cleaving RNA sequence from hepatitis 5 virus was modified to produce a ribozyme capable of catalyzing the cleavage of RNA in an intermolecular (trans) reaction. The 5-derived ribozyme cleaved substrate RNA at a specific site, and the sequence specificity could be altered with mutations in the region of the ribozyme proposed to base pair with thesubstrate. A substrate target size of approximately 8 nucleotides in length was identified. Octanucleotides containing a single ribonucleotide immediately 5'to the cleavage site were substrates for cleavage, and cleavage activity was significantly reduced only with a guanine base at that position. A deoxyribose 5'to the cleavage site blocked the reaction. These data are consistent with a proposed secondary structure for the self-cleaving form of the hepatitis 8 virus ribozyme in which a duplex forms with sequences 3'to the cleavage site, and they support a proposed mechanism in which cleavage involves attack on the phosphorus at the cleavage site by the adjacent 2'-hydroxyl group.Hepatitis 8 virus (HDV) 1 is a small single-stranded RNA virus that has been found in certain patients who are also infected with hepatitis B (Taylor, 1990). A self-cleaving se-quence present in both the genomic RNA and the complementary antigenomic RNA may act to process the RNA during rolling circle replication of the viral RNAs (Kuo et al., 1988; Sharmeen et al., 1988; Wu et al., 1989). The HDV RNA, therefore, may be the first clear example of an auto-catalytic RNA (ribozyme) that in its natural form functions in human cells. With the identificationof self-cleaving se-quences in the HDV RNAs (Kuo et al., 1988; Sharmeen et al., 1988; Wu et al., 1989), it was suggested that the HDV self-cleaving structure would haveto represent a structural motif distinct from other self-cleaving RNAs (Hutchins et al.,
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DOI：
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发表时间：
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期刊：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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