Hovlinc is a recently evolved class of ribozyme found in human lncRNA

Naturally-occurring catalytic RNA molecules — ribozymes — have attracted a great deal of research interest, yet very few of them have been identified in humans. Here, we developed a genome-wide approach to discover self-cleaving ribozymes and identified one naturally-occurring ribozyme in humans. The secondary structure and biochemical properties of this ribozyme indicate that it belongs to yet un-identified class of small self-cleaving ribozymes. The sequence of the ribozyme exhibits a clear evolutionary path from appearance between ~130 and ~65 million years ago (mya) to gain of self-cleavage activity very recently, ~13–10 mya, in the common ancestor of humans, chimpanzees and gorillas. The ribozyme appears to be functional in vivo and is embedded within an lncRNA belonging to the class of very long intergenic non-coding (vlinc) RNAs. The presence of a catalytic RNA enzyme in lncRNA opens a possibility that these transcripts could function by carrying catalytic RNA domains. Overall design: In identification of self-cleaving ribozyme, 9 samples were analyzed with 3 replicates each containing 2 control samples and 1 RppH&XRN-1 treated sample. To verify the cleavage site of hovlinc ribozyme, 1 sample containing self-cleavage products ligated to an RNA oligo was analyzed.