Functional conservation of lncRNAJPXdespite sequence and structural divergence

SummaryLong noncoding RNAs (lncRNAs) have been identified in all eukaryotes and are most abundant in the human genome. However, the functional importance and mechanisms of action for human lncRNAs are largely unknown. Using comparative sequence, structural, and functional analyses, we characterize the evolution and molecular function of human lncRNAJPX. We find that humanJPXand its mouse homolog, lncRNAJpx, have deep divergence in their nucleotide sequences and RNA secondary structures. Despite such differences, both lncRNAs demonstrate robust binding to CTCF, a protein that is central toJpx’s role in X chromosome inactivation. In addition, our functional rescue experiment usingJpx-deletion mutant cells, shows that humanJPXcan functionally complement the loss ofJpxin mouse embryonic stem cells. Our findings support a model for functional conservation of lncRNAs independent from sequence and structural changes. The study provides mechanistic insight into the evolution of lncRNA function.