Special Issue "Function and Structure of RNase P in Fungi, Bacteria and Human Cells"

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (31 January 2016)

Special Issue Editor

Guest Editor
Prof. Dr. Denis Drainas

Department of Biochemistry, School of Medicine, University of Patras, 1 Asklipiou st., 26504 Rio-Patras, Greece
Website | E-Mail
Interests: RNase P as a target for novel inhibitors; research and development of polyamine-acidic retinoid conjugates for use as antipsoriatic drugs; activation of the ribozyme RNase P for applications in the specialized silencing of gene expression

Special Issue Information

Dear Colleagues,

Ribonuclease P (RNase P) is an essential endonuclease that cleaves the 5' leader sequence of precursor tRNAs during their biogenesis. Almost all forms of RNase P contain a single RNA subunit, and one (in bacteria) or more (in archaea and eukaryotes) protein subunits. In bacteria, and in some archaea, the RNA subunit is a true trans-acting ribozyme, while in eukaryotes it retains traces of catalytic activity. Recently, in higher eukaryotes, a protein only form of RNase P in mitochondria and chloroplasts has been found.

RNase P is inhibited by many different kinds of inhibitors, like, protein synthesis inhibitors, retinoids, arotinoids, porphyrins, porphines, calcipotriol and anthralin. Due to its high diversity it could be served as a suitable target for the development of new drugs in the battle against bacterial drug resistance.

The finding that the minimal substrate requirements for RNase P activity is a structure equivalent to the upper part of a precursor tRNA allowed RNase P to be used as a tool for gene silencing. Endogenous RNase P directed by external guide sequences, or M1 RNA (the RNA subunit of E. coli RNase P) linked to a guide sequence (M1GS), can cleave any target RNA. This methodology makes RNase P an important tool for RNA-mediated therapeutics.

We look forward to reading your contributions,

Prof. Dr. Denis Drainas
Guest Editor

Manuscript Submission Information

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Published Papers (6 papers)

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Research

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Open AccessArticle Inhibition of Bacterial RNase P RNA by Phenothiazine Derivatives
Biomolecules 2016, 6(3), 38; doi:10.3390/biom6030038
Received: 30 June 2016 / Revised: 24 August 2016 / Accepted: 26 August 2016 / Published: 8 September 2016
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Abstract
There is a need to identify novel scaffolds and targets to develop new antibiotics. Methylene blue is a phenothiazine derivative, and it has been shown to possess anti-malarial and anti-trypanosomal activities. Here, we show that different phenothiazine derivatives and pyronine G inhibited the
[...] Read more.
There is a need to identify novel scaffolds and targets to develop new antibiotics. Methylene blue is a phenothiazine derivative, and it has been shown to possess anti-malarial and anti-trypanosomal activities. Here, we show that different phenothiazine derivatives and pyronine G inhibited the activities of three structurally different bacterial RNase P RNAs (RPRs), including that from Mycobacterium tuberculosis, with Ki values in the lower μM range. Interestingly, three antipsychotic phenothiazines (chlorpromazine, thioridazine, and trifluoperazine), which are known to have antibacterial activities, also inhibited the activity of bacterial RPRs, albeit with higher Ki values than methylene blue. Phenothiazines also affected lead(II)-induced cleavage of bacterial RPR and inhibited yeast tRNAPhe, indicating binding of these drugs to functionally important regions. Collectively, our findings provide the first experimental data showing that long, noncoding RNAs could be targeted by different phenothiazine derivatives. Full article
(This article belongs to the Special Issue Function and Structure of RNase P in Fungi, Bacteria and Human Cells)
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Review

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Open AccessReview Mechanistic and Structural Studies of Protein-Only RNase P Compared to Ribonucleoproteins Reveal the Two Faces of the Same Enzymatic Activity
Biomolecules 2016, 6(3), 30; doi:10.3390/biom6030030
Received: 19 May 2016 / Revised: 16 June 2016 / Accepted: 17 June 2016 / Published: 24 June 2016
Cited by 3 | PDF Full-text (1596 KB) | HTML Full-text | XML Full-text
Abstract
RNase P, the essential activity that performs the 5′ maturation of tRNA precursors, can be achieved either by ribonucleoproteins containing a ribozyme present in the three domains of life or by protein-only enzymes called protein-only RNase P (PRORP) that occur in eukaryote nuclei
[...] Read more.
RNase P, the essential activity that performs the 5′ maturation of tRNA precursors, can be achieved either by ribonucleoproteins containing a ribozyme present in the three domains of life or by protein-only enzymes called protein-only RNase P (PRORP) that occur in eukaryote nuclei and organelles. A fast growing list of studies has investigated three-dimensional structures and mode of action of PRORP proteins. Results suggest that similar to ribozymes, PRORP proteins have two main domains. A clear functional analogy can be drawn between the specificity domain of the RNase P ribozyme and PRORP pentatricopeptide repeat domain, and between the ribozyme catalytic domain and PRORP N4BP1, YacP-like Nuclease domain. Moreover, both types of enzymes appear to dock with the acceptor arm of tRNA precursors and make specific contacts with the corner of pre-tRNAs. While some clear differences can still be delineated between PRORP and ribonucleoprotein (RNP) RNase P, the two types of enzymes seem to use, fundamentally, the same catalytic mechanism involving two metal ions. The occurrence of PRORP and RNP RNase P represents a remarkable example of convergent evolution. It might be the unique witness of an ongoing replacement of catalytic RNAs by proteins for enzymatic activities. Full article
(This article belongs to the Special Issue Function and Structure of RNase P in Fungi, Bacteria and Human Cells)
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Figure 1

Open AccessReview The Diversity of Ribonuclease P: Protein and RNA Catalysts with Analogous Biological Functions
Biomolecules 2016, 6(2), 27; doi:10.3390/biom6020027
Received: 21 March 2016 / Revised: 4 May 2016 / Accepted: 6 May 2016 / Published: 13 May 2016
Cited by 4 | PDF Full-text (5476 KB) | HTML Full-text | XML Full-text
Abstract
Ribonuclease P (RNase P) is an essential endonuclease responsible for catalyzing 5’ end maturation in precursor transfer RNAs. Since its discovery in the 1970s, RNase P enzymes have been identified and studied throughout the three domains of life. Interestingly, RNase P is either
[...] Read more.
Ribonuclease P (RNase P) is an essential endonuclease responsible for catalyzing 5’ end maturation in precursor transfer RNAs. Since its discovery in the 1970s, RNase P enzymes have been identified and studied throughout the three domains of life. Interestingly, RNase P is either RNA-based, with a catalytic RNA subunit, or a protein-only (PRORP) enzyme with differential evolutionary distribution. The available structural data, including the active site data, provides insight into catalysis and substrate recognition. The hydrolytic and kinetic mechanisms of the two forms of RNase P enzymes are similar, yet features unique to the RNA-based and PRORP enzymes are consistent with different evolutionary origins. The various RNase P enzymes, in addition to their primary role in tRNA 5’ maturation, catalyze cleavage of a variety of alternative substrates, indicating a diversification of RNase P function in vivo. The review concludes with a discussion of recent advances and interesting research directions in the field. Full article
(This article belongs to the Special Issue Function and Structure of RNase P in Fungi, Bacteria and Human Cells)
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Open AccessReview Sequence Analysis and Comparative Study of the Protein Subunits of Archaeal RNase P
Biomolecules 2016, 6(2), 22; doi:10.3390/biom6020022
Received: 1 March 2016 / Revised: 5 April 2016 / Accepted: 8 April 2016 / Published: 20 April 2016
Cited by 1 | PDF Full-text (2226 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
RNase P, a ribozyme-based ribonucleoprotein (RNP) complex that catalyzes tRNA 5′-maturation, is ubiquitous in all domains of life, but the evolution of its protein components (RNase P proteins, RPPs) is not well understood. Archaeal RPPs may provide clues on how the complex evolved
[...] Read more.
RNase P, a ribozyme-based ribonucleoprotein (RNP) complex that catalyzes tRNA 5′-maturation, is ubiquitous in all domains of life, but the evolution of its protein components (RNase P proteins, RPPs) is not well understood. Archaeal RPPs may provide clues on how the complex evolved from an ancient ribozyme to an RNP with multiple archaeal and eukaryotic (homologous) RPPs, which are unrelated to the single bacterial RPP. Here, we analyzed the sequence and structure of archaeal RPPs from over 600 available genomes. All five RPPs are found in eight archaeal phyla, suggesting that these RPPs arose early in archaeal evolutionary history. The putative ancestral genomic loci of archaeal RPPs include genes encoding several members of ribosome, exosome, and proteasome complexes, which may indicate coevolution/coordinate regulation of RNase P with other core cellular machineries. Despite being ancient, RPPs generally lack sequence conservation compared to other universal proteins. By analyzing the relative frequency of residues at every position in the context of the high-resolution structures of each of the RPPs (either alone or as functional binary complexes), we suggest residues for mutational analysis that may help uncover structure-function relationships in RPPs. Full article
(This article belongs to the Special Issue Function and Structure of RNase P in Fungi, Bacteria and Human Cells)
Open AccessReview Trying on tRNA for Size: RNase P and the T-box Riboswitch as Molecular Rulers
Biomolecules 2016, 6(2), 18; doi:10.3390/biom6020018
Received: 23 February 2016 / Revised: 23 March 2016 / Accepted: 25 March 2016 / Published: 1 April 2016
Cited by 2 | PDF Full-text (2126 KB) | HTML Full-text | XML Full-text
Abstract
Length determination is a fundamental problem in biology and chemistry. Numerous proteins measure distances on linear biopolymers to exert effects with remarkable spatial precision. Recently, ruler-like devices made of noncoding RNAs have been structurally and biochemically characterized. Two prominent examples are the RNase
[...] Read more.
Length determination is a fundamental problem in biology and chemistry. Numerous proteins measure distances on linear biopolymers to exert effects with remarkable spatial precision. Recently, ruler-like devices made of noncoding RNAs have been structurally and biochemically characterized. Two prominent examples are the RNase P ribozyme and the T-box riboswitch. Both act as molecular calipers. The two RNAs clamp onto the elbow of tRNA (or pre-tRNA) and make distance measurements orthogonal to each other. Here, we compare and contrast the molecular ruler characteristics of these RNAs. RNase P appears pre-configured to measure a fixed distance on pre-tRNA to ensure the fidelity of its maturation. RNase P is a multiple-turnover ribozyme, and its rigid structure efficiently selects pre-tRNAs, cleaves, and releases them. In contrast, the T-box is flexible and segmented, an architecture that adapts to the intrinsically flexible tRNA. The tripartite T-box inspects the overall shape, anticodon sequence, and aminoacylation status of an incoming tRNA while it folds co-transcriptionally, leading to a singular, conditional genetic switching event. The elucidation of the structures and mechanisms of action of these two RNA molecular rulers may augur the discovery of new RNA measuring devices in noncoding and viral transcriptomes, and inform the design of artificial RNA rulers. Full article
(This article belongs to the Special Issue Function and Structure of RNase P in Fungi, Bacteria and Human Cells)
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Open AccessReview RNase P-Mediated Sequence-Specific Cleavage of RNA by Engineered External Guide Sequences
Biomolecules 2015, 5(4), 3029-3050; doi:10.3390/biom5043029
Received: 29 July 2015 / Revised: 16 October 2015 / Accepted: 29 October 2015 / Published: 9 November 2015
Cited by 3 | PDF Full-text (439 KB) | HTML Full-text | XML Full-text
Abstract
The RNA cleavage activity of RNase P can be employed to decrease the levels of specific RNAs and to study their function or even to eradicate pathogens. Two different technologies have been developed to use RNase P as a tool for RNA knockdown.
[...] Read more.
The RNA cleavage activity of RNase P can be employed to decrease the levels of specific RNAs and to study their function or even to eradicate pathogens. Two different technologies have been developed to use RNase P as a tool for RNA knockdown. In one of these, an external guide sequence, which mimics a tRNA precursor, a well-known natural RNase P substrate, is used to target an RNA molecule for cleavage by endogenous RNase P. Alternatively, a guide sequence can be attached to M1 RNA, the (catalytic) RNase P RNA subunit of Escherichia coli. The guide sequence is specific for an RNA target, which is subsequently cleaved by the bacterial M1 RNA moiety. These approaches are applicable in both bacteria and eukaryotes. In this review, we will discuss the two technologies in which RNase P is used to reduce RNA expression levels. Full article
(This article belongs to the Special Issue Function and Structure of RNase P in Fungi, Bacteria and Human Cells)

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