Multiple mTOR RNA localization signals regulate subcellular protein synthesis and axonal growth

Area of Science:

• Molecular Biology
• Neuroscience
• Genetics

Background:

• Subcellular localization of mTOR is critical for cell size and growth regulation.
• The distinct roles of mRNA versus protein localization in mTOR regulation remain unclear.

Purpose of the Study:

• To investigate the mechanisms of mTOR mRNA localization.
• To determine the impact of mTOR mRNA subcellular distribution on neuronal growth and body size.

Main Methods:

• Utilized reporter mRNA localization assays to identify mTOR Localizing Sequences (MLS).
• Generated gene-edited mice lacking specific 5'UTR and 3'UTR MLS.
• Analyzed body weight, brain size, and neuronal axonal protein synthesis.

Main Results:

• Identified two novel 5'UTR MLS in addition to the known 3'UTR MLS.
• Deletion of both 5'UTR MLS resulted in mTOR hypomorphic mice with reduced body weight and brain size.
• Mice lacking the second 5'UTR MLS and 3'UTR showed specific mTOR mislocalization to neuronal axons, impairing local protein synthesis and neuronal growth.

Conclusions:

• Multiple UTR sequences contribute to mTOR mRNA localization.
• Subcellular localization of mTOR mRNA is essential for regulating local protein synthesis and neuronal development.