Dicer-independent processing of small RNA duplexes: mechanistic insights and applications.

Elena Herrera-Carrillo, Ben Berkhout

Nucleic acids research 2017 Oct 13

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MicroRNAs (miRNAs) play a pivotal role in the regulation of cellular gene expression via the conserved RNA interference (RNAi) mechanism. Biogenesis of the unusual miR-451 does not require Dicer. This molecule is instead processed by the Argonaute 2 (Ago2) enzyme. Similarly, unconventional short hairpin RNA (shRNA) molecules have been designed as miR-451 mimics that rely exclusively on Ago2 for maturation. We will review recent progress made in the understanding of this alternative processing route. Next, we describe different Dicer-independent shRNA designs that have been developed and discuss their therapeutic advantages and disadvantages. As an example, we will present the route towards development of a durable gene therapy against HIV-1. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Citation

Elena Herrera-Carrillo, Ben Berkhout. Dicer-independent processing of small RNA duplexes: mechanistic insights and applications. Nucleic acids research. 2017 Oct 13;45(18):10369-10379