From alpaca to zebrafish: Hammerhead ribozymes wherever you look

Abstract

The hammerhead ribozyme was originally discovered in subviral plant pathogens and was subsequently also found in a few other genomic locations. Using a secondary structure-based descriptor, we have searched publicly accessible sequence databases for new examples of type III hammerhead ribozymes. The more than 60,000 entries fulfilling the descriptor were filtered with respect to folding and stability parameters that were experimentally validated. This resulted in a set of 284 unique motifs, of which 124 represent database entries of known hammerhead ribozymes from subviral plant pathogens and A. thaliana. The remainder are 160 novel ribozyme candidates in 50 different eukaryotic genomes. With a few exceptions, the ribozymes were found either in repetitive DNA sequences or in introns of protein coding genes. Our data, which is complementary to a study by De la Peñ a and García-Robles in 2010, indicate that the hammerhead is the most abundant small endonucleolytic ribozyme, which, in view of no sequence conservation beyond the essential nucleotides, likely has evolved independently in different organisms.

Intronic hammerhead ribozymes in mRNA biogenesis

“…Very similar type-I HHRs to these have been recently reported widespread in the genomes of the frog Xenopus tropicalis and the lamprey Petromyzon marinus ( Figure 2A) (De la Pe ñ a and Garc í a-Robles, 2010a ; Perreault et al , 2011 ;Seehafer et al , 2011 ). The major feature of this class of HHRs resides in their short and unstable helix III, which is usually capped by a palindromic loop.…”

“…Similar to the amphibian motifs, other genomic HHRs have been found to reside in DNA tandem repeats of carnation plants (Daros and Flores , 1995 ), schistosomes (Ferbeyre et al , 1998 ) and cave crickets (Rojas et al , 2000 ), suggesting a similar role for these genomic HHRs in the biology of such tandem-repetitive DNA. More recently, different bioinformatic approaches have uncovered a widespread occurrence of the HHR motif among all life kingdoms (De la Pe ñ a and Garc í a- Robles, 2010a,b ;Jimenez et al , 2011 ;Perreault et al , 2011 ;Seehafer et al , 2011 ; for a review see Hammann et al , 2012 ). Whereas most of the newly detected examples reinforce a role of the HHR in interspersed repetitive DNA, in some other cases, such as in bacteria (intergenic HHRs) or aminiotes (intronic HHRs), new and specific biological functions are hinted for this small catalytic RNA.…”

HDV-like self-cleaving ribozymes

“…These findings are in stark contrast with hammerhead ribozymes, which have a less complex fold, are also widely distributed in nature, and have been isolated several times in vitro. [45][46][47][48] Even though it is not yet clear how the HDV-like ribozymes evolved, the fact that they appear in such a widespread manner and varying biological roles, including retrotransposition and viral genome processing, suggests that they may be involved in many processes. Further analysis will surely reveal mechanisms by which these ribozymes are regulated and new pathways that are affected by their scission.…”

How RNA acts as a nuclease: some mechanistic comparisons in the nucleolytic ribozymes

“…Ligation is the reverse of this reaction (26)(27)(28)(29)(30), and occurs if the cleavage product RNA is held in place by the structure of the ribozyme. The hammerhead (31,32), hepatitis delta virus (HDV) (33,34) and twister (12) …”