Elavl3 is essential for the maintenance of Purkinje neuron axons

Abstract

Neuronal Elav-like (nElavl or neuronal Hu) proteins are RNA-binding proteins that regulate RNA stability and alternative splicing, which are associated with axonal and synaptic structures. nElavl proteins promote the differentiation and maturation of neurons via their regulation of RNA. The functions of nElavl in mature neurons are not fully understood, although Elavl3 is highly expressed in the adult brain. Furthermore, possible associations between nElavl genes and several neurodegenerative diseases have been reported. We investigated the relationship between nElavl functions and neuronal degeneration using Elavl3−/− mice. Elavl3−/− mice exhibited slowly progressive motor deficits leading to severe cerebellar ataxia, and axons of Elavl3−/− Purkinje cells were swollen (spheroid formation), followed by the disruption of synaptic formation of axonal terminals. Deficit in axonal transport and abnormalities in neuronal polarity was observed in Elavl3−/− Purkinje cells. These results suggest that nElavl proteins are crucial for the maintenance of axonal homeostasis in mature neurons. Moreover, Elavl3−/− mice are unique animal models that constantly develop slowly progressive axonal degeneration. Therefore, studies of Elavl3−/− mice will provide new insight regarding axonal degenerative processes.

Choice of Alternative Polyadenylation Sites, Mediated by the RNA-Binding Protein Elavl3, Plays a Role in Differentiation of Inhibitory Neuronal Progenitors

“…Drosophila Elav protein is mainly expressed in the insect neurons and has been shown to participate in their differentiation and axon guidance (Simionato et al, 2007; Colombrita et al, 2013). In mammals, Elavl2-4 proteins are also mainly expressed in neurons (Ogawa et al, 2018), but their functions is still to be explored.…”

Synergistic regulation of Rgs4 mRNA by HuR and miR-26/RISC in neurons

“…In addition to future studies addressing the combinatorial function of different RBPs as well as the miRNA/RISC machinery in brain through CLIP, it will be intriguing to get insight into the RBP-dependent dynamics of RNA structures in living cells [35]. To our current knowledge, the regulation of the AU-rich transcriptome in the brain has been studied solely through the neuronspecific Hu proteins HuB/C/D [36][37][38][39]. Only recently, the neuronal function of the ubiquitously expressed HuR has been explored [17][18][19]40,41].…”

Peer Review #1 of "The co-expression networks of differentially expressed RBPs with TFs and LncRNAs related to clinical TNM stages of cancers (v0.1)"

“…Elavl3 is closely related to neurodegenerative diseases and play an important role in maintaining the axonal homeostasis of neurons (Ogawa et al, 2018). HNRNPA1, regulated by miR-503 and miR-424, is associated with breast cancer cell proliferation (Otsuka, Yamamoto & Ochiya, 2018).…”