Distinct cis elements in the 3′ UTR of the C. elegans cebp-1 mRNA mediate its regulation in neuronal development

•3′ UTR of cebp-1 mRNA contains multiple regulatory elements.•A stem-loop like structure regulates cebp-1's translation in neurons.•Distinct 3′ UTR elements contributes to cebp-1 function in a context-dependent manner.•Multiple mechanisms control optimization of cebp-1 expression levels.

The 3′ untranslated regions (3′ UTRs) of mRNAs mediate post-transcriptional regulation of genes in many biological processes. Cis elements in 3′ UTRs can interact with RNA-binding factors in sequence-specific or structure-dependent manners, enabling regulation of mRNA stability, translation, and localization. Caenorhabditis elegans CEBP-1 is a conserved transcription factor of the C/EBP family, and functions in diverse contexts, from neuronal development and axon regeneration to organismal growth. Previous studies revealed that the levels of cebp-1 mRNA in neurons depend on its 3′ UTR and are also negatively regulated by the E3 ubiquitin ligase RPM-1. Here, by systematically dissecting cebp-1's 3′ UTR, we test the roles of specific cis elements in cebp-1 expression and function in neurons. We present evidence for a putative stem-loop in the cebp-1 3′ UTR that contributes to basal expression levels of mRNA and to negative regulation by rpm-1. Mutant animals lacking the endogenous cebp-1 3′ UTR showed a noticeable increased expression of cebp-1 mRNA and enhanced the neuronal developmental phenotypes of rpm-1 mutants. Our data reveal multiple cis elements within cebp-1's 3′ UTR that help to optimize CEBP-1 expression levels in neuronal development.