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Updated: Apr 4, 2026
Detection of Axonally Localized mRNAs in Brain Sections Using High-Resolution In Situ Hybridization
Published on: June 17, 2015
Multiple mTOR RNA localization signals regulate subcellular protein synthesis and axonal growth
Nitzan Samra1, Pabitra K Sahoo2,3, Agostina Di-Pizio1
1Departments of Biomolecular Sciences and Molecular Neuroscience, Weizmann Institute of Science; Rehovot, Israel.
Abstract:
Subcellular localization of mTOR is thought to be key for regulating cell size and growth, but the relative contributions of mRNA versus protein localization are unclear. We used reporter mRNA localization assays to identify two distinct mTOR Localizing Sequences (MLS) in its 5'UTR, in addition to the localization activity already reported for the 3'UTR. Gene-edited mice with deletion of both 5'UTR MLS are mTOR hypomorphs with reduced body weight and brain size. In contrast, a mouse line lacking the second 5'UTR MLS and the 3'UTR retains near normal overall mTOR expression levels with specific subcellular perturbation of mTOR localization to neuronal axons. This subcellular mTOR deficit affects axonal local protein synthesis and neuronal growth. Thus, mTOR transcripts are localized by multiple UTR sequences, and subcellular localization of mTOR mRNA regulates local protein synthesis and neuronal growth.
Insights
Messenger RNA (mRNA) localization of mTOR (mechanistic target of rapamycin) is crucial for cell growth. This study identifies specific sequences controlling mTOR mRNA transport, impacting neuronal development and body size.
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.
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