RNA editing of microRNA prevents RNA-induced silencing complex recognition of target mRNA

Area of Science:

• Molecular Biology
• Virology
• Genetics

Background:

• MicroRNAs (miRNAs) regulate gene expression by silencing target messenger RNAs (mRNAs) through the RNA-induced silencing complex (RISC).
• RNA editing can alter miRNA function, but its role within the RISC, particularly for viral miRNAs, remains underexplored.

Purpose of the Study:

• To investigate the function of edited viral microRNAs within the Argonaut (Ago) complex during white spot syndrome virus (WSSV) infection in Marsupenaeus japonicus shrimp.

Main Methods:

• Sequence analysis of the Ago complex from infected shrimp.
• Identification and characterization of edited viral miRNAs and their interactions with host and viral targets.

Main Results:

• Host adenosine deaminase acting on RNA (ADAR) catalyzed A-to-I RNA editing of a viral miRNA (WSSV-miR-N12) at the +16 site within the Ago complex.
• This non-seed editing did not disrupt miRNA-Ago association but inhibited miRNA binding to its target gene (wsv399).
• The targeted viral gene (wsv399) normally inhibits WSSV infection, thus its inhibition by edited miRNA leads to virus latency.

Conclusions:

• RNA editing of viral miRNA within the RISC is a novel mechanism for regulating viral infection.
• This process results in virus latency by preventing the edited miRNA from silencing its inhibitory target gene.