Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Oct 13;45(18):10369-10379.
doi: 10.1093/nar/gkx779.

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

Elena Herrera-Carrillo  1 , Ben Berkhout  1
Affiliations
Review

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

Elena Herrera-Carrillo et al. Nucleic Acids Res. .

Abstract

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Endogenous miRNA (A) and exogenous shRNA (B) processing pathways. The intracellular processing pathways are depicted starting from the endogenous miRNA gene in the cell or the transduced shRNA transgene cassette. The canonical Dicer-dependent and non-canonical Dicer-independent pathways are depicted for both molecules. Ago2 plays an essential role in the Dicer-independent pathways. See the text for further details.
Figure 2.
Figure 2.
Cartoon of the key features of a regular microRNA (miRNA, A), a Dicer-independent miRNA (miR-451, B), a Dicer-processed short hairpin RNA (shRNA, C), and several Dicer-independent shRNA designs in panels D–H: sshRNA: small shRNA, AgoshRNA: Ago2-dependent shRNA, sli-siRNA: Ago2-sliced siRNA agsiRNA: synthetic Ago2-sliced siRNA, agshRNA: Ago2-sliced shRNA and saiRNA: Ago2-processed interfering RNA. See the text for further details.
Figure 3.
Figure 3.
Cartoon of the key features of a Dicer-independent shRNA. See the text for further details.
See this image and copyright information in PMC

References

    1. Fire A., Xu S., Montgomery M.K., Kostas S.A., Driver S.E., Mello C.C.. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998; 391:806–811. - PubMed
    1. Napoli C., Lemieux C., Jorgensen R.. Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous genes in trans. Plant Cell. 1990; 2:279–289. - PMC - PubMed
    1. Bartel D.P. MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136:215–233. - PMC - PubMed
    1. Yi R., Qin Y., Macara I.G., Cullen B.R.. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003; 17:3011–3016. - PMC - PubMed
    1. Lund E., Guttinger S., Calado A., Dahlberg J.E., Kutay U.. Nuclear export of microRNA precursors. Science. 2004; 303:95–98. - PubMed

MeSH terms