Herrera-Carrillo Elena, Harwig Alex, Liu Ying Poi, Berkhout Ben
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
RNA. 2014 Sep;20(9):1410-8. doi: 10.1261/rna.043950.113. Epub 2014 Jul 17.
Recent evidence indicates the presence of alternative pathways for microRNA (miRNA) and short hairpin (shRNA) processing. Specifically, some of these molecules are refractory to Dicer-mediated processing, which allows alternative processing routes via the Ago2 endonuclease. The resulting RNA molecules differ in size and sequence and will thus trigger the silencing of different target RNAs. It is, therefore, important to understand these processing routes in mechanistic detail such that one can design exclusive RNA reagents for a specific processing route. The exact sh/miRNA properties that determine this routing toward Dicer or Ago2 are incompletely understood. The size of the base-paired stem seems an important determinant, but other RNA elements may contribute as well. In this study, we document the importance of a weak G-U or U-G base pair at the top of the hairpin stem.
最近的证据表明，存在微小RNA（miRNA）和短发夹RNA（shRNA）加工的替代途径。具体而言，其中一些分子对Dicer介导的加工具有抗性，这允许通过Ago2核酸内切酶进行替代加工途径。产生的RNA分子在大小和序列上有所不同，因此会触发不同靶RNA的沉默。因此，从机制细节上理解这些加工途径很重要，这样人们就可以为特定的加工途径设计专用的RNA试剂。决定这种向Dicer或Ago2的加工途径的确切sh/miRNA特性尚未完全了解。碱基配对茎的大小似乎是一个重要的决定因素，但其他RNA元件也可能起作用。在本研究中，我们证明了发夹茎顶部弱G-U或U-G碱基对的重要性。
