The long noncoding RNA CIRBIL is a regulator of steroidogenesis in mice.

ABSTRACT

Infertility affects roughly 8-12 % of couples worldwide, and in above 50 % of couples, male factors are the primary or contributing cause. Many long noncoding RNAs (lncRNAs) are detected in the testis, but their functions are not well understood. CIRBIL was 862 nucleotides in length and was found to be localized mostly in the cytosol of Leydig cell, a small portion was positioned inside the seminiferous tubules. Loss of CIRBIL in mice resulted in male subfertility, characterized by smaller testis and increased germ cell apoptosis. Deletion of CIRBIL significant decreased the number of sperm and impaired the integrity of sperm head and tail. In CIRBIL KO mice, testosterone levels in serum and expression of testosterone biosynthesis genes (STAR and 3ß-HSD) were both reduced. Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were primarily enriched in steroid synthesis process in CIRBIL-binding proteins. Protein-protein (PPI) interaction networks revealed that both cis- and trans-regulated target genes of CIRBIL were associated with testosterone synthesis. Collectively, our results strongly suggest that CIRBIL is a regulator of steroid hormone synthesis.