The ubiquitous hammerhead ribozyme

Abstract

The hammerhead ribozyme is a small catalytic RNA motif capable of endonucleolytic (self-) cleavage. It is composed of a catalytic core of conserved nucleotides flanked by three helices, two of which form essential tertiary interactions for fast selfscission under physiological conditions. Originally discovered in subviral plant pathogens, its presence in several eukaryotic genomes has been reported since. More recently, this catalytic RNA motif has been shown to reside in a large number of genomes. We review the different approaches in discovering these new hammerhead ribozyme sequences and discuss possible biological functions of the genomic motifs.

Intronic hammerhead ribozymes in mRNA biogenesis

“…A relationship with the biology of genetic mobile elements in eukaryotes has been advanced for both the HHR and the HDV-like ribozymes, either with non-autonomous SINE retroelements (Epstein and Gall , 1987 ;Ferbeyre et al , 1998 ;Rojas et al , 2000 ;Hammann et al , 2012 ) or with autonomous LINE retroelements (Eickbush and Eickbush , 2010 ;Ruminski et al , 2011 ), respectively. The similarities between both ribozymes seem to reach the genomes of higher vertebrates, where just a few examples of the two self-cleaving motifs have been so far detected as exceptionally conserved motifs (Salehi -Ashtiani et al, 2006 ; De la Pe ñ a and Garc í a-Robles, 2010a ).…”

“…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.…”

Re-characterization of hammerhead ribozymes as molecular tools for intermolecular RNA cleavage

“…1a). 6 One of the most prominent features of the HHRz is the three-dimensional interaction between the loop in stem II and the bulge in loop I, which is believed to enhance the catalytic activity of the HHRz. 7 The construction of the HHRz was subsequently devised from two independent molecules via splitting loop III which resulted in a transformation from intramolecular (cis-) cleavage to intermolecular (trans-) cleavage.…”

“…After checking all of the RNA sequences and repeating the cleavage reaction several times, we are sure about our results and finally find that the previous conclusion is inaccurate. 6,12,24,25 A tremendous amount of research has been conducted to investigate the properties of the hammerhead ribozyme in term of its function, [26][27][28] working conditions as well application in drug therapy, 19,22,29 which has been summarized in several nice reviews, 3,25 yet lots of basic information about the HHRz is ambiguous or even contradictory. As the hammerhead ribozyme has become an increasingly important tool for RNA manipulation, 30 a precise instruction is urgently required.…”

Sequence-controlled RNA self-processing: computational design, biochemical analysis, and visualization by AFM

“…This processing is dependent on specific RNA structural motifs that support reaction at the site of cleavage and ligation (Hampel and Tritz 1989;DeYoung et al 1995). Among those, the hammerhead and the hairpin ribozyme are probably the best studied small RNAs with catalytic activity (Hammann et al 2012;Müller et al 2012). …”