Abstract
Neurons are morphologically complex cells that rely on the compartmentalization of protein expression to develop and maintain their extraordinary cytoarchitecture. This formidable task is achieved, at least in part, by targeting mRNA to subcellular compartments where they are rapidly translated. mRNA transcripts are the conveyor of genetic information from DNA to the translational machinery, however, they are also endowed with additional functions linked to both the coding sequence (open reading frame, or ORF) and the flanking 5′ and 3′ untranslated regions (UTRs), that may harbor coding-independent functions. In this review, we will highlight recent evidences supporting new coding-dependent and -independent functions of mRNA and discuss how nuclear and cytoplasmic post-transcriptional modifications of mRNA contribute to localization and translation in mammalian cells with specific emphasis on neurons. We also describe recently developed techniques that can be employed to study RNA dynamics at subcellular level in eukaryotic cells in developing and regenerating neurons.
Highlights
RNA is the most ancient biological polymer whose existence is thought to date back to the prebiotic world
It is recognized that the 5 and 3 untranslated regions (UTRs) might exert a prominent regulatory role by both contributing to mRNA folding and providing ciselements that recruit RNA binding proteins necessary for transcript localization and translation. mRNA isoforms are generated by alternative splicing, which may include or exclude certain exons, Origins of RNA Isoforms Diversity in Neurons and alternative polyadenylation that generates transcripts with identical open reading frames (ORFs) but distinct 3 UTRs. mRNA can undergo post-transcriptional base modifications, such as adenosine methylation (Meyer and Jaffrey, 2014; Dominissini et al, 2016; Roundtree et al, 2017) and uridylation (Scheer et al, 2016), which may affect the ability of the transcript to transfer the information encoded by the ORF
The RNA stem-loops derived from the phage MS2 are recognized with high specificity and affinity by MS2 Coat Protein (MCP), such that if MCP is tagged with a fluorescent protein like GFP, the binding to multiple MS2 sequences located within the 3 UTR of interest allows the detection of single molecules of mRNA
Summary
RNA is the most ancient biological polymer whose existence is thought to date back to the prebiotic world. Additional BDNF isoforms are generated by the alternative usage of polyadenylation sites that give raise to transcripts with either short or long 3 UTRs, affecting differential subcellular localization in response to extrinsic stimuli (An et al, 2008; Will et al, 2013; Vicario et al, 2015). These data raise the interesting possibility that post-transcriptional nuclear splicing may represent an additional mechanism to control gene expression, how neuronal activation influences intron splicing and the impact of the newly translated isoforms on the proteome remain unknown.
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