MiR-10a* up-regulates coxsackievirus B3 biosynthesis by targeting the 3D-coding sequence.

MiR-10a* up-regulates coxsackievirus B3 biosynthesis by targeting the 3D-coding sequence.
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DOI:
10.1093/nar/gkt058
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发表时间:
2013-04-01
影响因子:
14.9
通讯作者:
Zhong Z
Zhong Z
中科院分区:
生物学2区
文献类型:
--
作者:
Tong L;Lin L;Wu S;Guo Z;Wang T;Qin Y;Wang R;Zhong X;Wu X;Wang Y;Luan T;Wang Q;Li Y;Chen X;Zhang F;Zhao W;Zhong Z

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microRNAs(miRNAs)是一类非编码小分子RNA,通过靶向信使RNA在转录后调控基因表达。在miRNA生物发生期间,星星链(miRNA*)通常在细胞中降解至低水平。然而,某些miRNA* 大量表达,并可被募集到沉默复合物中以调节基因表达。大多数miRNAs在基因表达中起抑制性调节剂的作用。B组柯萨奇病毒(CVB)是人类病毒性心肌炎和扩张型心肌病的主要病原体。CVB基因组是一种正义单链RNA。我们先前的研究表明miR-342- 5 p可以通过靶向其2C编码序列来抑制CVB的生物发生。在本研究中,我们发现miR-10a双链体可以显著上调CVB 3型(CVB 3)的生物合成。进一步的研究表明,正是miR-10 a星星链(miR-10 a *)促进了CVB 3的生物合成。定点突变显示miR-10a* 靶点位于病毒3D编码区的nt 6818-nt 6941序列。在哺乳Balb/c小鼠的心脏组织中可检测到miR-10a*,这表明miR-10a* 可能影响CVB 3在其心脏感染期间的复制。总之,这些数据首次表明miRNA* 可以正向调节基因表达。miR-10a* 可能参与了CVB 3的心脏发病机制。
MicroRNAs (miRNAs) are small non-coding RNAs that can posttranscriptionally regulate gene expression by targeting messenger RNAs. During miRNA biogenesis, the star strand (miRNA*) is generally degraded to a low level in the cells. However, certain miRNA* express abundantly and can be recruited into the silencing complex to regulate gene expression. Most miRNAs function as suppressive regulators on gene expression. Group B coxsackieviruses (CVB) are the major pathogens of human viral myocarditis and dilated cardiomyopathy. CVB genome is a positive-sense, single-stranded RNA. Our previous study shows that miR-342-5p can suppress CVB biogenesis by targeting its 2C-coding sequence. In this study, we found that the miR-10a duplex could significantly up-regulate the biosynthesis of CVB type 3 (CVB3). Further study showed that it was the miR-10a star strand (miR-10a*) that augmented CVB3 biosynthesis. Site-directed mutagenesis showed that the miR-10a* target was located in the nt6818–nt6941 sequence of the viral 3D-coding region. MiR-10a* was detectable in the cardiac tissues of suckling Balb/c mice, suggesting that miR-10a* may impact CVB3 replication during its cardiac infection. Taken together, these data for the first time show that miRNA* can positively modulate gene expression. MiR-10a* might be involved in the CVB3 cardiac pathogenesis.
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