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Nucleic Acid Ther. 2012 Feb;22(1):3-16. doi: 10.1089/nat.2011.0330. Epub 2012 Jan 27.

Argonaute and the nuclear RNAs: new pathways for RNA-mediated control of gene expression.

Author information

1
Departments of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.

Abstract

Small RNAs are a commonly used tool for gene silencing and a promising platform for nucleic acid drug development. They are almost exclusively used to silence gene expression post-transcriptionally through degradation of mRNA. Small RNAs, however, can have a broader range of function by binding to Argonaute proteins and associating with complementary RNA targets in the nucleus, including long noncoding RNAs (lncRNAs) and pre-mRNA. Argonaute-RNA complexes can regulate nuclear events like transcription, genome maintenance, and splicing. Thousands of lncRNAs and alternatively spliced pre-mRNA isoforms exist in humans, and these RNAs may serve as natural targets for regulation and therapeutic intervention. This review describes nuclear mechanisms for Argonaute proteins and small RNAs, new pathways for sequence-specific targeting, and the potential for therapeutic development of small RNAs with nuclear targets.

PMID:
22283730
PMCID:
PMC3318256
DOI:
10.1089/nat.2011.0330
[Indexed for MEDLINE]
Free PMC Article

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