Live cell imaging reveals 3′-UTR dependent mRNA sorting to synapses

• Published in: Nature communications 2019-07, Vol.10 (1), p.3178-13, Article 3178
• Main Authors: Bauer, Karl E., Segura, Inmaculada, Gaspar, Imre, Scheuss, Volker, Illig, Christin, Ammer, Georg, Hutten, Saskia, Basyuk, Eugénia, Fernández-Moya, Sandra M., Ehses, Janina, Bertrand, Edouard, Kiebler, Michael A.
• Format: Article
• Language: English
• Subjects: 13; 13/109; 14; 14/63; 3' Untranslated regions; 3' Untranslated Regions - genetics; 631/1647/245/2225; 631/337/1645/2052; 631/378/2591; 631/57/343/2281; 631/80/85; 64/86; 96/106; Animals; Anterograde transport; Bias; Cell Line; Chemical activity; Dendrites; Dendrites - genetics; HEK293 Cells; Hippocampus - metabolism; Humanities and Social Sciences; Humans; Life Sciences; mRNA; multidisciplinary; Neuromodulation; Organic chemistry; Rats; Rats, Sprague-Dawley; Recruitment; RGS Proteins - genetics; RNA transport; RNA Transport - physiology; RNA, Messenger - genetics; RNA-Binding Proteins - genetics; Science; Science (multidisciplinary); Synapses; Synapses - metabolism; Temporal resolution; Translation; Transport
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11123-x

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. Asymmetric subcellular mRNA distribution is important for local translation of neuronal mRNAs. Here the authors employed MS2 live-cell imaging and showed that the reporter mRNA containing the 3’ UTR of Rgs4 shows an anterograde transport bias, dependent on neuronal activity and the protein Staufen2, and mediates sustained mRNA recruitment to synapses.