Messenger RNAs bearing tRNA-like features exemplified by interferon alfa 5 mRNA

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• 作者：Rosa Díaz-Toledano ; Jordi Gómez
• 关键词：RNA mimicry ; RNase P ; IFNA ; CAR signal ; HCV IRES ; L ; shaped
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：72
• 期：19
• 页码：3747-3768
• 全文大小：6,134 KB
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• 作者单位：Rosa Díaz-Toledano (1) (2) (3)
  Jordi Gómez (1) (2)
  
  1. Laboratorio de Arqueología del RNA, Departamento de Bioquímica y Biología Molecular, Instituto de Parasitología y Biomedicina López Neyra (IPBLN-CSIC), Armilla, Granada, Spain
  2. Centro de Investigación Biológica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
  3. Centro de Biología Molecular Severo Ochoa (UAM-CSIC) Cantoblanco, Madrid, Spain
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Biomedicine
  Life Sciences
  Biochemistry
  
• 出版者：Birkh盲user Basel
• ISSN：1420-9071

文摘

The purpose of this work was to ascertain whether liver mRNA species share common structural features with hepatitis C virus (HCV) mRNA that allow them to support the RNase-P (pre-tRNA/processing enzyme) cleavage reaction in vitro. The presence of RNase-P competitive elements in the liver mRNA population was determined by means of biochemical techniques, and a set of sensitive mRNA species were identified through microarray screening. Cleavage specificity and substrate length requirement of around 200 nts, were determined for three mRNA species. One of these cleavage sites was found in interferon-alpha 5 (IFNA5) mRNA between specific base positions and with the characteristic RNase-P chemistry of cleavage. It was mapped within a cloverleaf-like structure revealed by a comparative structural analysis based on several direct enzymes and chemical probing methods of three RNA fragments of increasing size, and subsequently contrasted against site-directed mutants. The core region was coincident with the reported signal for the cytoplasmic accumulation region (CAR) in IFNAs. Striking similarities with the tRNA-like element of the antagonist HCV mRNA were found. In general, this study provides a new way of looking at a variety of viral tRNA-like motifs as this type of structural mimicry might be related to specific host mRNA species rather than, or in addition to, tRNA itself. Keywords RNA mimicry RNase P IFNA CAR signal HCV IRES L-shaped