GSE160025
Cytoplasmic cleavage of IMPA1 3'UTR is necessary for maintaining axon integrity.
The 3' untranslated regions (3'UTRs) of messenger RNAs (mRNA) are non-coding  sequences involved in many aspects of mRNA metabolism, including intracellular  localisation and translation. Incorrect processing and delivery of mRNA causes severe  developmental defects and has been implicated in many neurological disorders. Here,  we use deep sequencing to show that in sympathetic neuron axons, the 3'UTRs of  many transcripts undergo cleavage, generating isoforms that express the coding  sequence with a short 3'UTR, and stable 3'UTR-derived fragments of unknown  function. Cleavage of the long 3'UTR of Inositol Monophosphatase 1 ( IMPA1 ),  mediated by a protein complex containing the endonuclease Ago2 and the RNA  binding protein HuD, generates a translatable isoform that is necessary for maintaining  the integrity of sympathetic neuron axons. Thus, our study provides a new mechanism  of mRNA metabolism that simultaneously regulates local protein synthesis and  generates a yet undescribed class of non-coding RNAs. Overall design: Bulk 3' end sequencing data from cell body and distal axons of post-mitotic rat sympathetic neurons which distal axons have been exposed either to NGF or to NT3.