Influence of a 3' Terminal Ribozyme on AgoshRNA Biogenesis and Activity

Overview

Journal Mol Ther Nucleic Acids

Publisher Cell Press

Date 2019 May 4

PMID 31048184

Citations 3

Authors

Elena Herrera-Carrillo

Zongliang Gao

Ben Berkhout

Affiliations

Soon will be listed here.

Abstract

Short hairpin RNAs (shRNAs) can induce gene silencing via the RNA interference (RNAi) mechanism. We designed an alternative shRNA molecule with a relatively short base-paired stem that bypasses Dicer and instead is processed by the Argonaute 2 (Ago2) protein into a single guide RNA strand that effectively induces RNAi. We called these molecules AgoshRNAs. Active anti-HIV AgoshRNAs were developed, but their RNAi activity was generally reduced compared with the matching shRNAs. In an attempt to further optimize the AgoshRNA design, we inserted several self-cleaving ribozymes at the 3' terminus of the transcribed AgoshRNA and evaluated the impact on AgoshRNA processing and activity. The hepatitis delta virus (HDV) ribozyme is efficiently removed from the transcribed AgoshRNAs and generates a uniform 3' overhang, which translates into the enhanced antiviral activity of these molecules.

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