RT Journal Article
SR Electronic
T1 3’UTR Remodelling of Axonal Transcripts in Sympathetic Neurons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 170100
DO 10.1101/170100
A1 Catia Andreassi
A1 Raphaëlle Luisier
A1 Hamish Crerar
A1 Sasja Franke
A1 Nicholas M. Luscombe
A1 Giovanni Cuda
A1 Marco Gaspari
A1 Antonella Riccio
YR 2017
UL http://biorxiv.org/content/early/2017/07/30/170100.abstract
AB Asymmetric localization of mRNAs is a mechanism that constrains protein synthesis to subcellular compartments. In neurons, mRNA transcripts are transported to both dendrites and axons where they are rapidly translated in response to extracellular stimuli. To characterize the 3’ UTR isoforms localized in axons and cell bodies of sympathetic neurons we performed 3’ end-RNA sequencing. We discovered that isoforms transported to axons had significantly longer 3’ UTRs compared to cell bodies. Moreover, more than 100 short 3’ UTR isoforms were uniquely expressed in axons. Analysis of the long 3’ UTR of IMPA1 indicated that a multiprotein complex including Upf1, HuD and Ago2 mediated 3’ UTR cleavage. This event enhanced IMPA1 translation and was necessary for maintaining axon integrity. 3’ UTR cleavage took place in axons and was not limited to IMPA1 but extended to other transcripts with similar expression patterns. We conclude that the 3’ UTR of neuronal transcripts undergo post-transcriptional remodelling and describe an alternative mechanism that regulates local protein synthesis.HIGHLIGHTS3’end-Seq reveals distinct expression of alternative 3’UTR isoforms in axons and cell bodies of sympathetic neurons.Short 3’UTR isoforms uniquely detected in axons are generated in situ by cleavage of longer precursors.A protein complex containing Upf1, HuD, Pabpc4 and Ago2 mediates the cleavage of 3’UTRs.