New classes of self-cleaving ribozymes revealed by comparative genomics analysis

Weinberg, Zasha; Kim, Peter B; Chen, Tony H; Li, Sanshu; Harris, Kimberly A.; Lünse, Christina E.

doi:10.1038/nchembio.1846

Cited by 190 publications

(371 citation statements)

References 44 publications

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“…I shall refer to it here as the TS ribozyme. Weinberg et al (13) found that reaction rate increased with pH and exhibited a steep dependence on Mg 2+ ion concentration. No reaction was observed in 1M monovalent ions apart from very weak activity in Li + , and no cleavage occurred in Co(NH3)6 (III) ions.…”

Section: The Ts Ribozyme -A Probable Metalloenzymementioning

confidence: 99%

“…The rate of discovery of new ribozymes has recently increased significantly, as the Breaker laboratory bioinformatic pipeline has generated a flurry of new ribozymes (12,13). There are now nine distinct members of this group.…”

Section: The Nucleolytic Ribozymesmentioning

confidence: 99%

“…I shall also tentatively place the new pistol ribozyme (13,60) into the same group. The pH dependence of this ribozyme is similar to that of the hammerhead.…”

Section: The Hammerhead Ribozyme -The Role Of a 2'-hydroxyl Groupmentioning

confidence: 99%

“…The twister ribozyme (12) was the first of the new group that has emerged in the last few years from the Breaker lab bioinformatic pipeline (13). The secondary structure is that of a long stem-loop interrupted by internal loops that can form two tertiary interactions.…”

Section: Lilley : Ribozyme Mechanisms (Transactions Bst-2016-0158c) Rmentioning

confidence: 99%

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

Lilley

2017

Biochemical Society Transactions

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Section: The Ts Ribozyme -A Probable Metalloenzymementioning

confidence: 99%

Section: The Nucleolytic Ribozymesmentioning

confidence: 99%

“…I shall also tentatively place the new pistol ribozyme (13,60) into the same group. The pH dependence of this ribozyme is similar to that of the hammerhead.…”

Section: The Hammerhead Ribozyme -The Role Of a 2'-hydroxyl Groupmentioning

confidence: 99%

Section: Lilley : Ribozyme Mechanisms (Transactions Bst-2016-0158c) Rmentioning

confidence: 99%

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

Lilley

2017

Biochemical Society Transactions

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“…They comprise nine of the 14 different ribozyme classes that have been discovered to date. Among these are three self-cleaving ribozyme classes discovered only recently (Weinberg et al 2015) by exploiting the fact that some of the common self-cleaving ribozymes such as hammerhead (Perreault et al 2011;Hammann et al 2012), HDV (Webb and Lupták 2011), and twister (Roth et al 2014) frequently reside in the noncoding regions near particular types of genes. Specifically, a bioinformatics pipeline that employed comparative sequence and structural analysis algorithms was used to search for novel structured RNAs in a collection of noncoding regions near genes commonly associated with known self-cleaving ribozymes.…”

Section: Introductionmentioning

confidence: 99%

Biochemical analysis of hatchet self-cleaving ribozymes

Lünse

Harris

et al. 2015

RNA

Self Cite

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Hatchet RNAs are members of a novel self-cleaving ribozyme class that was recently discovered by using a bioinformatics search strategy. The consensus sequence and secondary structure of this class includes 13 highly conserved and numerous other modestly conserved nucleotides interspersed among bulges linking four base-paired substructures. A representative hatchet ribozyme from a metagenomic source requires divalent ions such as Mg 2+ to promote RNA strand scission with a maximum rate constant of ∼4 min −1 . As with all other small self-cleaving ribozymes discovered to date, hatchet ribozymes employ a general mechanism for catalysis involving the nucleophilic attack of a ribose 2 ′ -oxygen atom on an adjacent phosphorus center. Kinetic characteristics of the reaction demonstrate that members of this ribozyme class have an essential requirement for divalent metal ions and that they might have a complex active site that employs multiple catalytic strategies to accelerate RNA cleavage by internal phosphoester transfer.

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Catalytic RNA

Kent¹,

Burke²,

Lupták³

2021

Encyclopedia of Life Sciences

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RNA molecules have diverse roles in biological systems. While some code for proteins or act to translate codons to amino acids, others fold into specific shapes that endow them with the ability to catalyse specific chemical transformations. These catalytic RNAs, ribozymes, are responsible for protein synthesis, tRNA processing, self‐splicing of certain introns, self‐scission during rolling circle replication of some single‐stranded RNA viruses and cofactor‐dependent gene regulation in bacteria. Other ribozymes have been evolved in vitro to perform a wide variety of transformations. Two of these, tRNA aminoacylase and RNA polymerase ribozymes, are featured here because molecules with such capabilities are thought to have existed on early Earth, before proteins took over as the dominant biological catalysts. Most of the ribozymes have been shown to perform multiturnover catalysis and thus act as true enzymes, either in their natural, biological form or as engineered constructs. Key Concepts RNA molecules can fold into specific conformations and accelerate chemical transformations, thus acting as catalytic biomacromolecules, ribozymes. Ribozymes can accelerate chemical reactions by many orders of magnitude. Many ribozymes are capable of multiturnover catalysis, acting as enzymes. Protein synthesis templated by mRNA is catalysed by ribosomal RNA. Most ribozymes are phosphoryl transferases. In vitro selected ribozymes have been shown to catalyse a wide variety of reactions. The existence of ribozymes supports the RNA World hypothesis.

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New classes of self-cleaving ribozymes revealed by comparative genomics analysis

Cited by 190 publications

References 44 publications

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

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

Biochemical analysis of hatchet self-cleaving ribozymes

Catalytic RNA

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