Abstract
Kalirin, a key player in axonal development, nerve growth and synaptic re-modeling, is implicated in many pathological conditions like schizophrenia and autism-spectrum disorders. Alternative promoters and splicing lead to functionally distinct isoforms, but the post-transcriptional regulation of Kalirin has not been studied. Here, we report a novel non-coding RNA, which we name durga, arising from the first exon of kalirin a (kalrna) in the antisense orientation in zebrafish. The kalrna and durga transcripts are barely detectable during early development, but steadily increase by 24 hours post-fertilization (hpf) as the brain develops. Over-expression of durga in the zebrafish embryo led to an increase in kalrna expression. The morphology of the neurons cultured from durga injected embryos had significantly fewer and shorter dendrites. Although durga has no apparent sequence homolog in mammals, based on gene synteny, we found a non-coding RNA arising from the 5′ end of the human Kalrn gene and expressed in the human neuronal cell line, SH-SY5Y. We propose that the zebrafish lncRNA durga maintains dendritic length and density through regulation of kalrna expression and this may have further implications in mammalian systems.
Highlights
Development of the brain involves a fine balance between excitatory and inhibitory signaling at synapses, ensuring plasticity while avoiding excitotoxicity
Using a transgenic fish with neurons marked with kaede, we found that the ectopically injected lncRNA triggered a profound loss of dendrites, perhaps corresponding to the increased kalrna expression
In the zebrafish genome version 9 (Zv9) version of the zebrafish genome, mylk1 and kalrna were assembled in a convergent orientation on the same strand with ∼20 kb intergenic region
Summary
Development of the brain involves a fine balance between excitatory and inhibitory signaling at synapses, ensuring plasticity while avoiding excitotoxicity. Its binding to receptors leads to RhoGTPase mediated signaling and regulation of actin cytoskeletal organization. This intra-cellular signaling pathway leads to synaptic remodeling through altered dendrite numbers and dendritic morphology (Penzes et al, 2001). The Kalrn gene can code for a protein with a lipid binding motif, several tandem spectrin homology domains and additional protein-protein interaction domains like SH3 domain commonly found in members of signaling pathways (McPherson et al, 2002, 2004; Vishwanatha et al, 2012; Miller et al, 2017). The regulation of Kalrn transcription during development has not been explored extensively
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