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

ABSTRACT: 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’UTR. This 3’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’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 localisation and harbours ≥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’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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE132447 | GEO | 2021/01/21

REPOSITORIES: GEO

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