A Novel Long Non-coding RNA, durga Modulates Dendrite Density and Expression of kalirin in Zebrafish

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 <i>durga</i>, arising from the first exon of kalirin a (<i>kalrna</i>) in the antisense orientation in zebrafish. The <i>kalrna</i> and <i>durga</i> transcripts are barely detectable during early development, but steadily increase by 24 hours post-fertilization (hpf) as the brain develops. Over-expression of <i>durga</i> in the zebrafish embryo led to an increase in <i>kalrna</i> expression. The morphology of the neurons cultured from <i>durga</i> injected embryos had significantly fewer and shorter dendrites. Although <i>durga</i> 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 <i>Kalrn</i> gene and expressed in the human neuronal cell line, SH-SY5Y. We propose that the zebrafish lncRNA <i>durga</i> maintains dendritic length and density through regulation of <i>kalrna</i> expression and this may have further implications in mammalian systems.