Cytoplasmic cleavage of IMPA1 3′ UTR is necessary for maintaining axon integrity

The 3' untranslated regions (3' UTRs) of messenger RNAs (mRNAs) are non-coding sequences involved in many aspects of mRNA metabolism, including intracellular localization and translation. Incorrect processing and delivery of mRNA cause severe developmental defects and have 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 argonaute 2 (Ago2) generates a translatable isoform that is necessary for maintaining the integrity of sympathetic neuron axons. Thus, our study provides a mechanism of mRNA metabolism that simultaneously regulates local protein synthesis and generates an additional class of 3' UTR-derived RNAs.

Automated summary

The 3' untranslated regions (3' UTRs) of mRNA play essential roles in mRNA metabolism, with incorrect processing potentially leading to developmental defects and neurological disorders. Deep sequencing revealed cleavage of 3' UTRs in transcripts in sympathetic neuron axons, generating translatable isoforms crucial for axon integrity. This study provides insights into mRNA metabolism that regulates local protein synthesis and generates a new class of 3' UTR-derived RNAs.