Abstract
mRNA transport restricts translation to specific subcellular locations, which is the basis for many cellular functions. However, the precise process of mRNA sorting to synapses in neurons remains elusive. Here we use Rgs4 mRNA to investigate 3′-UTR-dependent transport by MS2 live-cell imaging. The majority of observed RNA granules display 3′-UTR independent bidirectional transport in dendrites. Importantly, the Rgs4 3′-UTR causes an anterograde transport bias, which requires the Staufen2 protein. Moreover, the 3′-UTR mediates dynamic, sustained mRNA recruitment to synapses. Visualization at high temporal resolution enables us to show mRNA patrolling dendrites, allowing transient interaction with multiple synapses, in agreement with the sushi-belt model. Modulation of neuronal activity by either chemical silencing or local glutamate uncaging regulates both the 3′-UTR-dependent transport bias and synaptic recruitment. This dynamic and reversible mRNA recruitment to active synapses would allow translation and synaptic remodeling in a spatially and temporally adaptive manner.
Highlights
MRNA transport restricts translation to specific subcellular locations, which is the basis for many cellular functions
Single molecule FISH40, targeting the MS2 repeats, demonstrated that the MS2+regulator of G protein signaling 4 (Rgs4) 3′-UTR reporter Messenger RNAs (mRNAs) localized to dendrites (Supplementary Fig. 1c), resembling endogenous Rgs[4] mRNA30
green fluorescent protein (GFP) fluorescence was clustered in discrete cytoplasmic granules that colocalized with MS2 Single molecule FISH (smFISH) signal (Fig. 1b, Supplementary Fig. 1e), confirming that we reliably detected reporter mRNAs, allowing the visualization of intracellular mRNA transport in living cells
Summary
MRNA transport restricts translation to specific subcellular locations, which is the basis for many cellular functions. Modulation of neuronal activity by either chemical silencing or local glutamate uncaging regulates both the 3′-UTR-dependent transport bias and synaptic recruitment This dynamic and reversible mRNA recruitment to active synapses would allow translation and synaptic remodeling in a spatially and temporally adaptive manner. Such active and directed transport has been hypothesized to be the driving force that mediates mRNA sorting to specific distal locations in neurons, such as postsynaptic sites or axonal growth cones, where it may become available for local translation[10,11,12,13,14,15] This allows the tightly regulated production of the resulting protein, both spatially and temporally. Silencing of Stau[2] induces a reduction of endogenous Rgs[4] mRNA both in vitro and in vivo, suggesting an involvement of Stau[2] in the regulation of Rgs[4] mRNA levels[30,34]
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