3’UTR cleavage of transcripts localized in axons of sympathetic neurons

Abstract

AbstractThe 3’ untranslated regions (3’UTRs) of messenger RNAs (mRNA) are non-coding sequences that regulate several aspects of mRNA metabolism, including intracellular localisation and translation. Here, we show that in sympathetic neuron axons, the 3’UTRs of many transcripts undergo cleavage, generating both translatable isoforms expressing a shorter 3’UTR, and 3’UTR fragments. 3’end RNA sequencing indicated that 3’UTR cleavage is a potentially widespread event in axons, which is mediated by a protein complex containing the endonuclease Ago2 and the RNA binding protein HuD. Analysis of the Inositol monophosphatase 1 (Impa1) mRNA revealed that a stem loop structure within the 3’UTR is necessary for Ago2 cleavage. Thus, remodeling of the 3’UTR provides an alternative mechanism that simultaneously regulates local protein synthesis and generates a new class of 3’UTR RNAs with yet unknown functions.