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Special Issue "Ribozymes and RNA Catalysis"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: closed (20 September 2016)

Special Issue Editor

Guest Editor
Prof. Dr. Sabine Müller

Institute of Biochemistry, Ernst-Moritz-Arndt-Universitat Greifswald
Website | E-Mail
Interests: nucleic acids chemistry; oligonucleotide synthesis; DNA/RNA functionalization; riboswitches; ribozymes; RNA engineering; RNA modification; RNA vaccines; RNA world

Special Issue Information

Dear Colleagues,

After the discovery of the first naturally occurring catalytic RNAs, more than 30 years ago, research in the field of ribozymes and RNA catalysis has made tremendous progress. In the 1990, most of the catalytic RNAs known today were identified in nature, and at the same time the powerful SELEX method (Systematic Evolution of Ligands by Exponential Enrichment) allowed the development of artificial ribozymes with rather diverse functionality. Over the years, investigation into the structure and mechanism of ribozymes led to a deep understanding of the catalytic strategies. Today, ribozymes are understood to an extent that allows rational design and engineering into catalytic RNAs with pre-defined function. However, there is still much to be learned. New ribozymes or novel genomic locations of known motifs in highly diverse genetic contexts in all branches of life are expected to be discovered by the help of high-throughput bioinformatics approaches. This Special Issue aims to provide a source of information on the ongoing discovery, characterization, engineering and application of ribozymes, and their biological functions.

Sabine Müller
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • aptazymes
  • bioinformatics
  • conformational analysis
  • co-transcriptional scission
  • engineering
  • in vitro selection
  • mechanism
  • metal ions
  • retrotransposon
  • ribosome
  • RNA cleavage
  • RNA folding
  • RNA ligation
  • RNA processing
  • RNA structure
  • roling circle replication
  • SELEX
  • Spliceosome
  • splicing
  • therapeutic RNA

Published Papers (9 papers)

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Editorial

Jump to: Research, Review

Open AccessEditorial Special Issue: Ribozymes and RNA Catalysis
Molecules 2017, 22(5), 789; doi:10.3390/molecules22050789
Received: 9 May 2017 / Revised: 9 May 2017 / Accepted: 11 May 2017 / Published: 11 May 2017
PDF Full-text (153 KB) | HTML Full-text | XML Full-text
Abstract
Over the past 35 years, RNA has become a molecule of utmost interest for researchers in the life sciences. The many functions that RNA fulfills in the cellular machinery have been elucidated with constant progress, revealing a complex network of RNA-mediated regulation of
[...] Read more.
Over the past 35 years, RNA has become a molecule of utmost interest for researchers in the life sciences. The many functions that RNA fulfills in the cellular machinery have been elucidated with constant progress, revealing a complex network of RNA-mediated regulation of key processes in the cellular life cycle [...]
Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)

Research

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Open AccessArticle Could a Proto-Ribosome Emerge Spontaneously in the Prebiotic World?
Molecules 2016, 21(12), 1701; doi:10.3390/molecules21121701
Received: 20 September 2016 / Revised: 21 November 2016 / Accepted: 24 November 2016 / Published: 9 December 2016
Cited by 4 | PDF Full-text (1071 KB) | HTML Full-text | XML Full-text
Abstract
An indispensable prerequisite for establishing a scenario of life emerging by natural processes is the requirement that the first simple proto-molecules could have had a realistic probability of self-assembly from random molecular polymers in the prebiotic world. The vestige of the proto-ribosome, which
[...] Read more.
An indispensable prerequisite for establishing a scenario of life emerging by natural processes is the requirement that the first simple proto-molecules could have had a realistic probability of self-assembly from random molecular polymers in the prebiotic world. The vestige of the proto-ribosome, which is believed to be still embedded in the contemporary ribosome, is used to assess the feasibility of such spontaneous emergence. Three concentric structural elements of different magnitudes, having a dimeric nature derived from the symmetrical region of the ribosomal large subunit, were suggested to constitute the vestige of the proto-ribosome. It is assumed to have materialized spontaneously in the prebiotic world, catalyzing non-coded peptide bond formation and simple elongation. Probabilistic and energetic considerations are applied in order to evaluate the suitability of the three contenders for being the initial proto-ribosome. The analysis points to the simplest proto-ribosome, comprised of a dimer of tRNA-like molecules presently embedded in the core of the symmetrical region, as the only one having a realistic statistical likelihood of spontaneous emergence from random RNA chains. Hence it offers a feasible starting point for a continuous evolutionary path from the prebiotic matter, through natural processes, into the intricate modern translation system. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Open AccessFeature PaperArticle Accumulation of Stable Full-Length Circular Group I Intron RNAs during Heat-Shock
Molecules 2016, 21(11), 1451; doi:10.3390/molecules21111451
Received: 20 September 2016 / Revised: 25 October 2016 / Accepted: 27 October 2016 / Published: 31 October 2016
Cited by 3 | PDF Full-text (3553 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Group I introns in nuclear ribosomal RNA of eukaryotic microorganisms are processed by splicing or circularization. The latter results in formation of full-length circular introns without ligation of the exons and has been proposed to be active in intron mobility. We applied qRT-PCR
[...] Read more.
Group I introns in nuclear ribosomal RNA of eukaryotic microorganisms are processed by splicing or circularization. The latter results in formation of full-length circular introns without ligation of the exons and has been proposed to be active in intron mobility. We applied qRT-PCR to estimate the copy number of circular intron RNA from the myxomycete Didymium iridis. In exponentially growing amoebae, the circular introns are nuclear and found in 70 copies per cell. During heat-shock, the circular form is up-regulated to more than 500 copies per cell. The intron harbours two ribozymes that have the potential to linearize the circle. To understand the structural features that maintain circle integrity, we performed chemical and enzymatic probing of the splicing ribozyme combined with molecular modeling to arrive at models of the inactive circular form and its active linear counterpart. We show that the two forms have the same overall structure but differ in key parts, including the catalytic core element P7 and the junctions at which reactions take place. These differences explain the relative stability of the circular species, demonstrate how it is prone to react with a target molecule for circle integration and thus supports the notion that the circular form is a biologically significant molecule possibly with a role in intron mobility. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Open AccessArticle Real-Time Detection of a Self-Replicating RNA Enzyme
Molecules 2016, 21(10), 1310; doi:10.3390/molecules21101310
Received: 6 September 2016 / Revised: 25 September 2016 / Accepted: 27 September 2016 / Published: 30 September 2016
Cited by 1 | PDF Full-text (1215 KB) | HTML Full-text | XML Full-text
Abstract
A system was developed to detect the self-replication of an RNA enzyme in real time. The enzyme is an RNA ligase that undergoes exponential amplification at a constant temperature and can be made to operate in a ligand-dependent manner. The real-time system is
[...] Read more.
A system was developed to detect the self-replication of an RNA enzyme in real time. The enzyme is an RNA ligase that undergoes exponential amplification at a constant temperature and can be made to operate in a ligand-dependent manner. The real-time system is based on a fluorimetric readout that directly couples the ligation event to an increase in florescence signal that can be monitored using standard instrumentation. The real-time system can also operate entirely with l-RNA, which is not susceptible to degradation by ribonucleases that are present in biological samples. The system is analogous to real-time PCR, but with the potential to detect small molecules, proteins, and other targets that can be recognized by a suitable aptamer. The ligand-dependent self-replication of RNA has potential applications in molecular diagnostics and biosensing that benefit from the rapid, precise, and real-time detection of various target molecules. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Open AccessArticle Group I Intron Internal Guide Sequence Binding Strength as a Component of Ribozyme Network Formation
Molecules 2016, 21(10), 1293; doi:10.3390/molecules21101293
Received: 17 August 2016 / Revised: 22 September 2016 / Accepted: 23 September 2016 / Published: 27 September 2016
Cited by 4 | PDF Full-text (1918 KB) | HTML Full-text | XML Full-text
Abstract
Origins-of-life research requires searching for a plausible transition from simple chemicals to larger macromolecules that can both hold information and catalyze their own production. We have previously shown that some group I intron ribozymes possess the ability to help synthesize other ribozyme genotypes
[...] Read more.
Origins-of-life research requires searching for a plausible transition from simple chemicals to larger macromolecules that can both hold information and catalyze their own production. We have previously shown that some group I intron ribozymes possess the ability to help synthesize other ribozyme genotypes by recombination reactions in small networks in an autocatalytic fashion. By simplifying these recombination reactions, using fluorescent anisotropy, we quantified the thermodynamic binding strength between two nucleotides of two group I intron RNA fragments for all 16 possible genotype combinations. We provide evidence that the binding strength (KD) between the 3-nucleotide internal guide sequence (IGS) of one ribozyme and its complement in another is correlated to the catalytic ability of the ribozyme. This work demonstrates that one can begin to deconstruct the thermodynamic basis of information in prebiotic RNA systems. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Review

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Open AccessReview Structural and Biochemical Properties of Novel Self-Cleaving Ribozymes
Molecules 2017, 22(4), 678; doi:10.3390/molecules22040678
Received: 27 November 2016 / Revised: 7 April 2017 / Accepted: 13 April 2017 / Published: 24 April 2017
Cited by 3 | PDF Full-text (2595 KB) | HTML Full-text | XML Full-text
Abstract
Fourteen well-defined ribozyme classes have been identified to date, among which nine are site-specific self-cleaving ribozymes. Very recently, small self-cleaving ribozymes have attracted renewed interest in their structure, biochemistry, and biological function since the discovery, during the last three years, of four novel
[...] Read more.
Fourteen well-defined ribozyme classes have been identified to date, among which nine are site-specific self-cleaving ribozymes. Very recently, small self-cleaving ribozymes have attracted renewed interest in their structure, biochemistry, and biological function since the discovery, during the last three years, of four novel ribozymes, termed twister, twister sister, pistol, and hatchet. In this review, we mainly address the structure, biochemistry, and catalytic mechanism of the novel ribozymes. They are characterized by distinct active site architectures and divergent, but similar, biochemical properties. The cleavage activities of the ribozymes are highly dependent upon divalent cations, pH, and base-specific mutations, which can cause changes in the nucleotide arrangement and/or electrostatic potential around the cleavage site. It is most likely that a guanine and adenine in close proximity of the cleavage site are involved in general acid-base catalysis. In addition, metal ions appear to play a structural rather than catalytic role although some of their crystal structures have shown a direct metal ion coordination to a non-bridging phosphate oxygen at the cleavage site. Collectively, the structural and biochemical data of the four newest ribozymes could contribute to advance our mechanistic understanding of how self-cleaving ribozymes accomplish their efficient site-specific RNA cleavages. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Open AccessReview The Hammerhead Ribozyme: A Long History for a Short RNA
Molecules 2017, 22(1), 78; doi:10.3390/molecules22010078
Received: 30 November 2016 / Revised: 28 December 2016 / Accepted: 29 December 2016 / Published: 4 January 2017
Cited by 5 | PDF Full-text (2366 KB) | HTML Full-text | XML Full-text
Abstract
Small nucleolytic ribozymes are a family of naturally occurring RNA motifs that catalyse a self-transesterification reaction in a highly sequence-specific manner. The hammerhead ribozyme was the first reported and the most extensively studied member of this family. However, and despite intense biochemical and
[...] Read more.
Small nucleolytic ribozymes are a family of naturally occurring RNA motifs that catalyse a self-transesterification reaction in a highly sequence-specific manner. The hammerhead ribozyme was the first reported and the most extensively studied member of this family. However, and despite intense biochemical and structural research for three decades since its discovery, the history of this model ribozyme seems to be far from finished. The hammerhead ribozyme has been regarded as a biological oddity typical of small circular RNA pathogens of plants. More recently, numerous and new variations of this ribozyme have been found to inhabit the genomes of organisms from all life kingdoms, although their precise biological functions are not yet well understood. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Open AccessReview Design and Experimental Evolution of trans-Splicing Group I Intron Ribozymes
Molecules 2017, 22(1), 75; doi:10.3390/molecules22010075
Received: 28 September 2016 / Revised: 27 December 2016 / Accepted: 29 December 2016 / Published: 2 January 2017
Cited by 1 | PDF Full-text (1865 KB) | HTML Full-text | XML Full-text
Abstract
Group I intron ribozymes occur naturally as cis-splicing ribozymes, in the form of introns that do not require the spliceosome for their removal. Instead, they catalyze two consecutive trans-phosphorylation reactions to remove themselves from a primary transcript, and join the two
[...] Read more.
Group I intron ribozymes occur naturally as cis-splicing ribozymes, in the form of introns that do not require the spliceosome for their removal. Instead, they catalyze two consecutive trans-phosphorylation reactions to remove themselves from a primary transcript, and join the two flanking exons. Designed, trans-splicing variants of these ribozymes replace the 3′-portion of a substrate with the ribozyme’s 3′-exon, replace the 5′-portion with the ribozyme’s 5′-exon, or insert/remove an internal sequence of the substrate. Two of these designs have been evolved experimentally in cells, leading to variants of group I intron ribozymes that splice more efficiently, recruit a cellular protein to modify the substrate’s gene expression, or elucidate evolutionary pathways of ribozymes in cells. Some of the artificial, trans-splicing ribozymes are promising as tools in therapy, and as model systems for RNA evolution in cells. This review provides an overview of the different types of trans-splicing group I intron ribozymes that have been generated, and the experimental evolution systems that have been used to improve them. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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Open AccessReview Many Activities, One Structure: Functional Plasticity of Ribozyme Folds
Molecules 2016, 21(11), 1570; doi:10.3390/molecules21111570
Received: 6 October 2016 / Revised: 12 November 2016 / Accepted: 14 November 2016 / Published: 18 November 2016
Cited by 4 | PDF Full-text (861 KB) | HTML Full-text | XML Full-text
Abstract
Catalytic RNAs, or ribozymes, are involved in a number of essential biological processes, such as replication of RNA genomes and mobile genetic elements, RNA splicing, translation, and RNA degradation. The function of ribozymes requires the formation of active sites decorated with RNA functional
[...] Read more.
Catalytic RNAs, or ribozymes, are involved in a number of essential biological processes, such as replication of RNA genomes and mobile genetic elements, RNA splicing, translation, and RNA degradation. The function of ribozymes requires the formation of active sites decorated with RNA functional groups within defined three-dimensional (3D) structures. The genotype (sequence) of RNAs ultimately determines what 3D structures they adopt (as a function of their environmental conditions). These 3D structures, in turn, give rise to biochemical activity, which can further elaborate them by catalytic rearrangements or association with other molecules. The fitness landscape of a non-periodic linear polymer, such as RNA, relates its primary structure to a phenotype. Two major challenges in the analysis of ribozymes is to map all possible genotypes to their corresponding catalytic activity (that is, to determine their fitness landscape experimentally), and to understand whether their genotypes and three-dimensional structures can support multiple different catalytic functions. Recently, the combined results of experiments that employ in vitro evolution methods, high-throughput sequencing and crystallographic structure determination have hinted at answers to these two questions: while the fitness landscape of ribozymes is rugged, meaning that their catalytic activity cannot be optimized by a smooth trajectory in sequence space, once an RNA achieves a stable three-dimensional fold, it can be endowed with distinctly different biochemical activities through small changes in genotype. This functional plasticity of highly structured RNAs may be particularly advantageous for the adaptation of organisms to drastic changes in selective pressure, or for the development of new biotechnological tools. Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
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