Pirakitikulr Nathan, Kohlway Andrew, Lindenbach Brett D, Pyle Anna M
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
Department of Microbial Pathogenesis, Yale University, New Haven, CT 06519, USA.
Mol Cell. 2016 Apr 7;62(1):111-20. doi: 10.1016/j.molcel.2016.01.024. Epub 2016 Feb 25.
RNA is a versatile macromolecule that accommodates functional information in primary sequence and secondary and tertiary structure. We use a combination of chemical probing, RNA structure modeling, comparative sequence analysis, and functional assays to examine the role of RNA structure in the hepatitis C virus (HCV) genome. We describe a set of conserved but functionally diverse structural RNA motifs that occur in multiple coding regions of the HCV genome, and we demonstrate that conformational changes in these motifs influence specific stages in the virus' life cycle. Our study shows that these types of structures can pervade a genome, where they play specific mechanistic and regulatory roles, constituting a "code within the code" for controlling biological processes.
RNA是一种多功能大分子,其一级序列以及二级和三级结构中都包含功能信息。我们结合化学探针法、RNA结构建模、比较序列分析和功能测定,来研究RNA结构在丙型肝炎病毒(HCV)基因组中的作用。我们描述了一组存在于HCV基因组多个编码区域的保守但功能多样的结构性RNA基序,并证明这些基序的构象变化会影响病毒生命周期中的特定阶段。我们的研究表明,这些类型的结构可遍布基因组,在其中发挥特定的机制和调节作用,构成控制生物过程的“密码中的密码”。