Nuclear processing of the 3′-end of pre-mRNA is crucial for the production of mature RNA and for the generation of the 3′ untranslated region. It is, therefore, involved in the post-transcriptional regulation of gene expression. However, the developmental role of this processing pathway is unclear. On p. 2237, Yishi Jin and colleagues now reveal that pre-mRNA 3′-end processing regulates synapse and axon development in C. elegans. In a genetic enhancer screen for synaptogenesis mutants, they identify Synaptic defective enhancer-1 (SYDN-1), a novel polyproline-rich protein required for synapse and axon development that localises to distinct nuclear regions. In a genetic suppressor screen, they discover that loss of function of Polyadenylation factor subunit-2, which interacts with the pre-mRNA 3′-end processing machinery, suppresses the neuronal defects of sydn-1 mutants. Furthermore, lack of sydn-1 increases 3′-end processing activity, and inactivation of several members of the pre-mRNA 3′-end processing machinery suppresses sydn-1 mutants. Thus, pre-mRNA 3′-end processing plays an important regulatory role during neuronal development.

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