Identification of long noncoding RNAs in injury-resilient and injury-susceptible mouse retinal ganglion cells

Abstract

Background Emerging evidence indicates that long noncoding RNAs (lncRNAs) are important regulators of various biological processes, and their expression can be altered following certain pathological conditions, including central nervous system injury. Retinal ganglion cells (RGCs), whose axons form the optic nerve, are a heterogeneous population of neurons with more than 40 molecularly distinct subtypes in mouse. While most RGCs, including the ON-OFF direction-selective RGCs (ooDSGCs), are vulnerable to axonal injury, a small population of RGCs, including the intrinsically photosensitive RGCs (ipRGCs), are more resilient. Results By performing systematic analyses on RNA-sequencing data, here we identify lncRNAs that are expressed in ooDSGCs and ipRGCs with and without axonal injury. Our results reveal a repertoire of different classes of lncRNAs, including long intergenic noncoding RNAs and antisense ncRNAs that are differentially expressed between these RGC types. Strikingly, we also found dozens of lncRNAs whose expressions are altered markedly in response to axonal injury, some of which are expressed exclusively in either one of the types. Moreover, analyses into these lncRNAs unraveled their neighboring coding genes, many of which encode transcription factors and signaling molecules, suggesting that these lncRNAs may act in cis to regulate important biological processes in these neurons. Lastly, guilt-by-association analysis showed that lncRNAs are correlated with apoptosis associated genes, suggesting potential roles for these lncRNAs in RGC survival. Conclusions Overall, the results of this study reveal RGC type-specific expression of lncRNAs and provide a foundation for future investigation of the function of lncRNAs in regulating neuronal type specification and survival.

The landscape of the long non-coding RNAs in developing mouse retinas

“…In addition, our previous work indicated the RGC-specific expression of three lincRNAs ( linc-3a , -3b , and − 3c ) through fluorescence in situ hybridization (FISH). More recently, Ayupe et al investigated the lncRNA expression in injury-resilient (ipRGCs) and injury-susceptible RGCs (ooDSGCs) and revealed the subtype-specific expression of a large proportion of lncRNAs, i.e., 31% (268/851) and 49% (564/1147) in ipRGCs and ooDSGCs, respectively [ 25 ]. Together these demonstrated high specificity of lncRNA expression at the levels of tissue subset, as well as neuron type and subtype, and suggested the critical regulatory roles of lncRNAs in retina development.…”

The landscape of the long non-coding RNAs in developing mouse retinas

“…In addition, our previous work indicated the RGC-speci c expression of three lincRNAs (linc-3a, -3b, and -3c) through uorescence in situ hybridization (FISH). More recently, Ayupe et al investigated the lncRNA expression in injury-resilient (ipRGCs) and injury-susceptible RGCs (ooDSGCs) and revealed the subtype-speci c expression of a large proportion of lncRNAs, i.e., 31% (268/851) and 49% (564/1147) in ipRGCs and ooDSGCs, respectively [25]. Together these demonstrated high speci city of lncRNA expression at the levels of tissue subset, as well as neuron type and subtype, and suggested the critical regulatory roles of lncRNAs in retina development.…”