Dendritic targeted mRNA expression via a cis-acting RNA UTR element

Area of Science:

• Neuroscience
• Molecular Biology
• Virology

Background:

• Local translation in neuronal neurites is crucial for synaptic plasticity.
• Targeted gene expression in neurites remains a significant challenge in neuroscience research.

Purpose of the Study:

• To evaluate the efficacy of the Tick-borne encephalitis virus (TBEV) 5 egular-UTR as a cis-acting RNA element for neurite-specific mRNA targeting.
• To develop a novel system for precise, localized protein expression in neuronal processes.

Main Methods:

• The TBEV 5 egular-UTR and the Actb 3 egular-UTR were tested for their ability to direct mRNA (mCherry CDS) to neurites.
• Adeno-associated virus (AAV) vectors were constructed using the TBEV 5 egular-UTR for in vivo studies.
• Neuronal cultures and in vivo models were used to assess protein expression and localization.

Main Results:

• Both TBEV 5 egular-UTR and Actb 3 egular-UTR facilitated mRNA transport to neurites, with TBEV 5 egular-UTR showing more robust targeting.
• No significant cytotoxicity was observed with the TBEV 5 egular-UTR in neuronal cells.
• In vivo AAV-mediated gene delivery resulted in enhanced mCherry protein expression in neurites of infected neurons.

Conclusions:

• The TBEV 5 egular-UTR is a highly efficient and short cis-acting RNA element suitable for neurite-specific gene expression.
• This system holds promise for advancing neural system research by enabling precise local expression of synaptic proteins.