RNase P
Encyclopedia
Ribonuclease P is a type of ribonuclease
which cleaves RNA
. RNase P is unique from other RNases in that it is a ribozyme
– a ribonucleic acid that acts as a catalyst in the same way that a protein
based enzyme would. Its function is to cleave off an extra, or precursor, sequence of RNA on tRNA molecules. Further RNase P is one of two known multiple turnover ribozymes in nature (the other being the ribosome
), the discovery of which earned Sidney Altman
and Thomas Cech
the Nobel Prize in Chemistry
in 1989: in the 1970s, Altman discovered the existence of precursor tRNA with flanking sequences and was the first to characterize RNase P and its activity in processing of the 5' leader sequence of precursor tRNA. Recent findings also reveal that RNase P has a new function . It has been shown that human nuclear RNase P is required for the normal and efficient transcription of various small noncoding RNA genes
, such as tRNA, 5S rRNA
, SRP
RNA and U6 snRNA
genes , which are transcribed by RNA polymerase III
, one of three major nuclear RNA polymerases in human cells.
l RNase P has two components: an RNA chain, called M1 RNA, and a polypeptide chain, or protein, called C5 protein. In vivo
, both components are necessary for the ribozyme to function properly, but in vitro
, the M1 RNA can act alone as a catalyst . The primary role of the C5 protein is to enhance the substrate binding affinity and the catalytic rate of the M1 RNA enzyme probably by increasing the metal ion affinity in the active site. The crystal structure of a bacterial RNase P holoenzyme with tRNA has been recently resolved, showing how the large, coaxially stacked helical domains of the RNase P RNA engage in shape selective recognition of the pre-tRNA target. This crystal structure confirms earlier models of substrate recognition and catalysis, identifies the location of the active site, and shows how the protein component increases RNase P functionality.
, RNase P ribonucleoprotein
s consist of 4-5 protein subunits that are associated with RNA. As revealed by in vitro reconstitution experiments these protein subunits are individually dispensable for tRNA processing that is essentially mediated by the RNA component. The structures of protein subunits of archaeal RNase P have been resolved by x-ray
crystallography and NMR
, thus revealing new protein domains and folding fundamental for function.
Isolated eukaryotic and archaeal RNase P RNA has not been shown to retain its catalytic function, but is still essential for the catalytic activity of the holoenzyme. Although the archaeal and eukaryotic holoenzymes have a much greater protein content than the bacterial ones, the RNA cores from all the three lineages are homologous -- helices corresponding to P1, P2, P3, P4, and P10/11 are common to all cellular RNase P RNAs. Yet, there is considerable sequence variation, particularly among the eukaryotic RNAs.
It has recently been argued that the archaebacteriium Nanoarchaeum equitans does not possess RNase P. Computational and experimental studies failed to find evidence for its existence. In this organism the tRNA promoter is close to the tRNA gene and it is thought that transcription starts at the first base of the tRNA thus removing the requirement for RNase P.
, most RNase P consists of an RNA chain that is structurally similar to that found in bacteria as well as nine to ten associated proteins (as opposed to the single bacterial RNase P protein, C5) . Five of these protein subunits exhibit homology to archaeal counterparts. These protein subunits of RNase P are shared with RNase MRP
, a catalytic ribonucleoprotein involved in processing of ribosomal RNA in the nucleolus
. RNase P from eukaryotes was only recently demonstrated to be a ribozyme . Accordingly, the numerous protein subunits of eucaryal RNase P have a minor contribution to tRNA processing per se , while they seem to be essential for the function of RNase P and RNase MRP in other biological settings, such as gene transcription and the cell cycle
. It has recently been discovered that human mitochondrial RNase P is a protein
and does not contain RNA
.
Ribonuclease
Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...
which cleaves RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
. RNase P is unique from other RNases in that it is a ribozyme
Ribozyme
A ribozyme is an RNA molecule with a well defined tertiary structure that enables it to catalyze a chemical reaction. Ribozyme means ribonucleic acid enzyme. It may also be called an RNA enzyme or catalytic RNA. Many natural ribozymes catalyze either the hydrolysis of one of their own...
– a ribonucleic acid that acts as a catalyst in the same way that a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
based enzyme would. Its function is to cleave off an extra, or precursor, sequence of RNA on tRNA molecules. Further RNase P is one of two known multiple turnover ribozymes in nature (the other being the ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
), the discovery of which earned Sidney Altman
Sidney Altman
Sidney Altman is a Canadian American molecular biologist, who is currently the Sterling Professor of Molecular, Cellular, and Developmental Biology and Chemistry at Yale University. In 1989 he shared the Nobel Prize in Chemistry with Thomas R...
and Thomas Cech
Thomas Cech
Thomas Robert Cech is a chemist who shared the 1989 Nobel prize in chemistry with Sidney Altman, for their discovery of the catalytic properties of RNA. Cech discovered that RNA could itself cut strands of RNA, which showed that life could have started as RNA...
the Nobel Prize in Chemistry
Nobel Prize in Chemistry
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
in 1989: in the 1970s, Altman discovered the existence of precursor tRNA with flanking sequences and was the first to characterize RNase P and its activity in processing of the 5' leader sequence of precursor tRNA. Recent findings also reveal that RNase P has a new function . It has been shown that human nuclear RNase P is required for the normal and efficient transcription of various small noncoding RNA genes
Non-coding RNA
A non-coding RNA is a functional RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA , non-messenger RNA and functional RNA . The term small RNA is often used for short bacterial ncRNAs...
, such as tRNA, 5S rRNA
5S ribosomal RNA
5S ribosomal RNA is a component of the large ribosomal subunit in both prokaryotes and eukaryotes .Eukaryotic 5S rRNA is synthesised by RNA polymerase III, whereas most other eukaroytic rRNAs are cleaved from a 45S precursor transcribed by RNA polymerase I...
, SRP
Signal recognition particle
The signal recognition particle is an abundant, cytosolic, universally conserved ribonucleoprotein that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes....
RNA and U6 snRNA
U6 spliceosomal RNA
U6 snRNA is the non-coding small nuclear RNA component of U6 snRNP , an RNA-protein complex that combines with other snRNPs, unmodified pre-mRNA, and various other proteins to assemble a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs...
genes , which are transcribed by RNA polymerase III
RNA polymerase III
RNA polymerase III transcribes DNA to synthesize ribosomal 5S rRNA, tRNA and other small RNAs. The genes transcribed by RNA Pol III fall in the category of "housekeeping" genes whose expression is required in all cell types and most environmental conditions...
, one of three major nuclear RNA polymerases in human cells.
In bacteria
BacteriaBacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l RNase P has two components: an RNA chain, called M1 RNA, and a polypeptide chain, or protein, called C5 protein. In vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
, both components are necessary for the ribozyme to function properly, but in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
, the M1 RNA can act alone as a catalyst . The primary role of the C5 protein is to enhance the substrate binding affinity and the catalytic rate of the M1 RNA enzyme probably by increasing the metal ion affinity in the active site. The crystal structure of a bacterial RNase P holoenzyme with tRNA has been recently resolved, showing how the large, coaxially stacked helical domains of the RNase P RNA engage in shape selective recognition of the pre-tRNA target. This crystal structure confirms earlier models of substrate recognition and catalysis, identifies the location of the active site, and shows how the protein component increases RNase P functionality.
Bacterial RNase P class A and B
Ribonuclease P (RNase P) is a ubiquitous endoribonuclease, found in archaea, bacteria and eukarya as well as chloroplasts and mitochondria. Its best characterised activity is the generation of mature 5'-ends of tRNAs by cleaving the 5'-leader elements of precursor-tRNAs. Cellular RNase Ps are ribonucleoproteins. RNA from bacterial RNase Ps retains its catalytic activity in the absence of the protein subunit, i.e. it is a ribozyme. Isolated eukaryotic and archaeal RNase P RNA has not been shown to retain its catalytic function, but is still essential for the catalytic activity of the holoenzyme. Although the archaeal and eukaryotic holoenzymes have a much greater protein content than the bacterial ones, the RNA cores from all the three lineages are homologous -- helices corresponding to P1, P2, P3, P4, and P10/11 are common to all cellular RNase P RNAs. Yet, there is considerable sequence variation, particularly among the eukaryotic RNAs.In archaea
In archaeaArchaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
, RNase P ribonucleoprotein
Ribonucleoprotein
Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...
s consist of 4-5 protein subunits that are associated with RNA. As revealed by in vitro reconstitution experiments these protein subunits are individually dispensable for tRNA processing that is essentially mediated by the RNA component. The structures of protein subunits of archaeal RNase P have been resolved by x-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
crystallography and NMR
NMR
NMR may refer to:Applications of Nuclear Magnetic Resonance:* Nuclear magnetic resonance* NMR spectroscopy* Solid-state nuclear magnetic resonance* Protein nuclear magnetic resonance spectroscopy* Proton NMR* Carbon-13 NMR...
, thus revealing new protein domains and folding fundamental for function.
Isolated eukaryotic and archaeal RNase P RNA has not been shown to retain its catalytic function, but is still essential for the catalytic activity of the holoenzyme. Although the archaeal and eukaryotic holoenzymes have a much greater protein content than the bacterial ones, the RNA cores from all the three lineages are homologous -- helices corresponding to P1, P2, P3, P4, and P10/11 are common to all cellular RNase P RNAs. Yet, there is considerable sequence variation, particularly among the eukaryotic RNAs.
It has recently been argued that the archaebacteriium Nanoarchaeum equitans does not possess RNase P. Computational and experimental studies failed to find evidence for its existence. In this organism the tRNA promoter is close to the tRNA gene and it is thought that transcription starts at the first base of the tRNA thus removing the requirement for RNase P.
In eukaryotes
In eukaryotes, such as humans and yeastYeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
, most RNase P consists of an RNA chain that is structurally similar to that found in bacteria as well as nine to ten associated proteins (as opposed to the single bacterial RNase P protein, C5) . Five of these protein subunits exhibit homology to archaeal counterparts. These protein subunits of RNase P are shared with RNase MRP
RNase MRP
RNase MRP is an enzymatically active ribonucleoprotein with two distinct roles in eukaryotes. In mitochondria it plays a direct role in the initiation of mitochondrial DNA replication. In the nucleus it is involved in precursor rRNA processing, where it cleaves the internal transcribed spacer 1...
, a catalytic ribonucleoprotein involved in processing of ribosomal RNA in the nucleolus
Nucleolus
The nucleolus is a non-membrane bound structure composed of proteins and nucleic acids found within the nucleus. Ribosomal RNA is transcribed and assembled within the nucleolus...
. RNase P from eukaryotes was only recently demonstrated to be a ribozyme . Accordingly, the numerous protein subunits of eucaryal RNase P have a minor contribution to tRNA processing per se , while they seem to be essential for the function of RNase P and RNase MRP in other biological settings, such as gene transcription and the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
. It has recently been discovered that human mitochondrial RNase P is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
and does not contain RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
.
External links
- RNase P Database at ncsu.edu