title: ELAV proteins along evolution: back to the nucleus?
abstract: The complex interplay of post-transcriptional regulatory mechanisms mediated by RNA-binding proteins (RBP) at different steps of RNA metabolism is pivotal for the development of the nervous system and the maintenance of adult brain activities. In this review, we will focus on the highly conserved ELAV gene family encoding for neuronal-specific RBPs which are necessary for proper neuronal differentiation and important for synaptic plasticity process. In the evolution from Drosophila to man, ELAV proteins seem to have changed their biological functions in relation to their different subcellular localization. While in Drosophila, they are localized in the nuclear compartment of neuronal cells and regulate splicing and polyadenylation, in mammals, the neuronal ELAV proteins are mainly present in the cytoplasm where they participate in regulating mRNA target stability, translation and transport into neurites. However, recent data indicate that the mammalian ELAV RBPs also have nuclear activities, similarly to their fly counterpart, being them able to continuously shuttle between the cytoplasm and the nucleus. Here, we will review and comment on all the biological functions associated with neuronal ELAV proteins along evolution and will show that the post-transcriptional regulatory network mediated by these RBPs in the brain is highly complex and only at an initial stage of being fully understood. This article is part of a Special Issue entitled 'RNA and splicing regulation in neurodegeneration'.
authors: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Via Zucchi, 18, 20095 Cusano Milanino (Milan), Italy; Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, "Dino Ferrari" Center, Università degli Studi di Milano, Via Sforza, 35, 20122 Milan, Italy.
authors: Claudia
authors: C
authors: Colombrita
authors: Vincenzo
authors: V
authors: Silani
authors: Antonia
authors: A
authors: Ratti
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks; D006801:Humans; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional
chemical_list: D051959:ELAV Proteins; D012313:RNA
keywords: ARE; AU-binding factor 1; AU-rich element; AUBF; AUF1; CARM1; CGRP; CPEB; CPSF160; CstF64; ELAV; FMRP; GAP-43; HDAC2; KH-type splicing regulatory protein; KSRP; PABP; PKCα; Polyadenylation; Post-transcriptional regulation; RBP; RNA recognition motif; RNA-binding protein; RNA-binding protein 9; RRM; SMN; Splicing; T-cell intracellular antigen-1; TAR DNA-binding protein 43; TDP-43; TIA-1; TIA-1-related protein; TIAR-1; TTP; UTR; ZBP1; adenosine–uridine binding factor; calcitonin gene-related peptide; cleavage and polyadenylation specificity factor 160 subunit; cleavage stimulation factor 64 subunit; coactivator-associated arginine methyltransferase 1; cytoplasmic polyadenylation element binding; eiF4A; elav; embryonic lethal abnormal vision; eukaryotic initiation factor 4A; fne; found in neurons; fragile X mental retardation protein; growth-associated protein 43; histone deacetylase 2; mRNA stability; miRNA; microRNA; polyA-binding protein; protein kinase C α; rbp9; survival of motoneurons; tristetrapolin; untranslated region; zipcode binding protein1