Human Lantern Ribozymes: Smallest Known Self-cleaving Ribozymes

Abstract

AbstractDespite their importance in a wide range of living organisms, self-cleaving ribozymes in human genome are few and poorly studied. Here, we performed deep mutational scanning and covariance analysis of two previously proposed self-cleaving ribozymes (LINE-1 and OR4K15 ribozymes). We found that the functional regions for both ribozymes are made of two short segments, connected by a non-functional loop with a total of 46 and 47 contiguous nucleotides only. The discovery makes them the shortest known self-cleaving ribozymes. Moreover, the above functional regions of LINE-1 and OR4K15 ribozymes are circular permutated with two nearly identical catalytic internal loops, supported by two stems of different lengths. This new self-cleaving ribozyme family, named as lantern ribozyme for their shape, is similar to the catalytic core region of the twister sister ribozymes in term of sequence and secondary structure. However, the nucleotides at the cleavage sites have shown that mutational effects on lantern ribozymes are different from twister sister ribozymes. Lacking a stem loop for stabilizing the core active region and two mismatches in the internal loops may force lantern ribozymes to adopt a tertiary structure (and functional mechanisms) different from twister sister, requiring further studies. Nevertheless, the discovery of the lantern ribozymes reveals a new ribozyme family with the simplest and, perhaps, the most primitive structure needed for self-cleavage.