Origin of a novel CYP20A1 lncRNA through 23 Alu exaptations in the human lineage creates a potential multi-miRNA sponge

Alu repeats contribute to lineage specific novelties in conserved transcriptional regulatory networks. We report for the first time the origin of a multi-miRNA human specific sponge through exaptation of 23 Alu repeats that forms a novel principal isoform of CYP20A1 gene with a 9kb 3 prime UTR. This 3 prime UTR, confirmed by RACE, is an outlier in terms of its length, with expression in multiple cell lines including brain as evidenced from single nucleus RNA-seq data of ~16000 human cortical neurons. It has diverged from its parent gene through exon skipping into a novel lncRNA. Its uniqueness in humans was validated by its presence in rosehip neurons and absence in closely related primate species through RNA-seq datasets. Strikingly, prediction by miRanda revealed ~4700 MREs for ~1000 different miRNAs, majorly in Alu repeats, in this 3 prime UTR. Permutations on 1000 random sets suggest their creation is non-random and post Alu exaptation. We hypothesise this lncRNA is an miRNA sponge as it has cytosolic localization and harbors greater than or equal to 10 MREs for 140 miRNAs (threshold > -25kcal/mol). Under experimental conditions where CYP20A1 displays differential expression, we probed the expression of the miRNAs that map to this 3 prime UTR and their cognate targets through small RNA and mRNA-seq, respectively. We observed correlated expression of our lncRNA and a set of 380 genes with downregulation in heat shock and upregulation in HIV1-Tat treatment in primary neurons. GO analyses suggest the involvement of this sponge lncRNA in modulation of processes linked to neuronal development and hemostasis pathways.