Ribonuclease (commonly abbreviated RNase) is a type of

nuclease A nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds between nucleotides of nucleic acids. Nucleases variously effect single and double stranded breaks in their ta ...

that catalyzes the degradation of

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

into smaller components. Ribonucleases can be divided into

endoribonuclease An endoribonuclease is a ribonuclease endonuclease. It cleaves either single-stranded or double-stranded RNA, depending on the enzyme. Example includes both single proteins such as RNase III, RNase A, RNase T1, RNase T2 and RNase H and also complex ...

s and

exoribonuclease An exoribonuclease is an exonuclease ribonuclease, which are enzymes that degrade RNA by removing terminal nucleotides from either the 5' end or the 3' end of the RNA molecule. Enzymes that remove nucleotides from the 5' end are called ''5'-3 ...

s, and comprise several sub-classes within the EC 2.7 (for the phosphorolytic enzymes) and 3.1 (for the hydrolytic enzymes) classes of enzymes.

Function

All organisms studied contain many RNases of two different classes, showing that RNA degradation is a very ancient and important process. As well as clearing of cellular RNA that is no longer required, RNases play key roles in the maturation of all RNA molecules, both messenger RNAs that carry genetic material for making proteins and non-coding RNAs that function in varied cellular processes. In addition, active RNA degradation systems are the first defense against RNA viruses and provide the underlying machinery for more advanced cellular immune strategies such as

RNAi RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by o ...

. Some cells also secrete copious quantities of non-specific RNases such as A and T1. RNases are, therefore, extremely common, resulting in very short lifespans for any RNA that is not in a protected environment. It is worth noting that all intracellular RNAs are protected from RNase activity by a number of strategies including 5' end capping, 3' end

polyadenylation Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In euk ...

, formation of an RNA·RNA duplex, and folding within an RNA protein complex (

ribonucleoprotein Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating in ...

particle or RNP). Another mechanism of protection is

ribonuclease inhibitor Ribonuclease inhibitor (RI) is a large (~450 residues, ~49 kDa), acidic (pI ~4.7), leucine-rich repeat protein that forms extremely tight complexes with certain ribonucleases. It is a major cellular protein, comprising ~0.1% of all cellular prot ...

(RI), which comprises a relatively large fraction of cellular protein (~0.1%) in some cell types, and which binds to certain ribonucleases with the highest affinity of any protein-protein interaction; the

dissociation constant In chemistry, biochemistry, and pharmacology, a dissociation constant (K_D) is a specific type of equilibrium constant that measures the propensity of a larger object to separate (dissociate) reversibly into smaller components, as when a complex fa ...

for the RI-RNase A complex is ~20 fM under physiological conditions. RI is used in most laboratories that study RNA to protect their samples against degradation from environmental RNases. Similar to

restriction enzyme A restriction enzyme, restriction endonuclease, REase, ENase or'' restrictase '' is an enzyme that cleaves DNA into fragments at or near specific recognition sites within molecules known as restriction sites. Restriction enzymes are one class o ...

s, which cleave highly specific sequences of double-stranded DNA, a variety of

s that recognize and cleave specific sequences of single-stranded RNA have been recently classified. RNases play a critical role in many biological processes, including

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

and

self-incompatibility Self-incompatibility (SI) is a general name for several genetic mechanisms that prevent self-fertilization in sexually reproducing organisms, and thus encourage outcrossing and allogamy. It is contrasted with separation of sexes among individuals ...

flowering plant Flowering plants are plants that bear flowers and fruits, and form the clade Angiospermae (), commonly called angiosperms. The term "angiosperm" is derived from the Greek words ('container, vessel') and ('seed'), and refers to those plants th ...

s (angiosperms). Many stress-response toxins of prokaryotic

toxin-antitoxin system A toxin-antitoxin system is a set of two or more closely linked genes that together encode both a "toxin" protein and a corresponding "antitoxin". Toxin-antitoxin systems are widely distributed in prokaryotes, and organisms often have them in mult ...

s have been shown to have RNase activity and

homology Homology may refer to: Sciences Biology *Homology (biology), any characteristic of biological organisms that is derived from a common ancestor * Sequence homology, biological homology between DNA, RNA, or protein sequences *Homologous chrom ...

Classification

Major types of endoribonucleases

* :

RNase A Pancreatic ribonuclease family (, ''RNase'', ''RNase I'', ''RNase A'', ''pancreatic RNase'', ''ribonuclease I'', ''endoribonuclease I'', ''ribonucleic phosphatase'', ''alkaline ribonuclease'', ''ribonuclease'', ''gene S glycoproteins'', ''Ceratit ...

is an RNase that is commonly used in research. RNase A (''e.g.'', bovine pancreatic ribonuclease A: ) is one of the hardiest enzymes in common laboratory usage; one method of isolating it is to boil a crude cellular extract until all enzymes other than RNase A are denatured. It is specific for single-stranded RNAs. It cleaves the 3'-end of unpaired C and U residues, ultimately forming a 3'-phosphorylated product via a 2',3'-cyclic monophosphate intermediate. It does not require any cofactors for its activity * :

RNase H Ribonuclease H (abbreviated RNase H or RNH) is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/ DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearly ...

is a ribonuclease that cleaves the RNA in a DNA/RNA duplex to produce ssDNA. RNase H is a non-specific endonuclease and catalyzes the cleavage of RNA via a hydrolytic mechanism, aided by an enzyme-bound divalent metal ion. RNase H leaves a 5'-phosphorylated product. * :

RNase III Ribonuclease III (RNase III or RNase C)(BREND3.1.26.3 is a type of ribonuclease that recognizes dsRNA and cleaves it at specific targeted locations to transform them into mature RNAs. These enzymes are a group of endoribonucleases that are chara ...

is a type of ribonuclease that cleaves rRNA (16s rRNA and 23s rRNA) from transcribed polycistronic RNA operon in prokaryotes. It also digests double strands RNA (dsRNA)-Dicer family of RNAse, cutting pre-miRNA (60–70bp long) at a specific site and transforming it in miRNA (22–30bp), that is actively involved in the regulation of transcription and mRNA life-time. * EC number 3.1.26.-??:

RNase L Ribonuclease L or RNase L (for ''latent''), known sometimes as ribonuclease 4 or 2'-5' oligoadenylate synthetase-dependent ribonuclease — is an interferon (IFN)-induced ribonuclease which, upon activation, destroys all RNA within the cell (bot ...

is an interferon-induced nuclease that, upon activation, destroys all RNA within the cell * :

RNase P Ribonuclease P (, ''RNase 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 f ...

is a type of ribonuclease that is unique in that it is a

ribozyme Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonst ...

– a

ribonucleic acid Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

that acts as a catalyst in the same way as an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

. One of its functions is to cleave off a leader sequence from the 5' end of one stranded pre-

tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...

. RNase P is one of two known multiple turnover ribozymes in nature (the other being the

ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...

). In bacteria RNase P is also responsible for the catalytic activity of holoenzymes, which consist of an apoenzyme that forms an active enzyme system by combination with a coenzyme and determines the specificity of this system for a substrate. A form of RNase P that is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

and does not contain RNA has recently been discovered. * EC number 3.1.??:

RNase PhyM RNase PhyM is a type of endoribonuclease An endoribonuclease is a ribonuclease endonuclease. It cleaves either single-stranded or double-stranded RNA, depending on the enzyme. Example includes both single proteins such as RNase III, RNase A, R ...

is sequence specific for single-stranded RNAs. It cleaves 3'-end of unpaired A and U residues. * :

RNase T1 Ribonuclease (commonly abbreviated RNase) 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 ...

is sequence specific for single-stranded RNAs. It cleaves 3'-end of unpaired G residues. * :

RNase T2 Ribonuclease T2 is an enzyme that in humans is encoded by the ''RNASET2'' gene. It is a type of endoribonuclease An endoribonuclease is a ribonuclease endonuclease. It cleaves either single-stranded or double-stranded RNA, depending on the enzyme ...

is sequence specific for single-stranded RNAs. It cleaves 3'-end of all 4 residues, but preferentially 3'-end of As. * : RNase U2 is sequence specific for single-stranded RNAs. It cleaves 3'-end of unpaired A residues. * : RNase V is specific for polyadenine and polyuridine RNA. * : RNase E is a ribonuclease of plant origin, which modulates SOS responses in bacteria, for a response to the stress of DNA damage by activation of the SOS mechanism by the RecA/LexA dependent signal transduction pathway that transcriptionally depresses a multiplicity of genes leading to transit arrest of cell division as well as initiation of DNA repair. * : RNase G It is involved in processing the 16'-end of the 5s rRNA. It is related to chromosome separation and cell division. It is considered one of the components of cytoplasmic axial filament bundles. It is also thought that it can regulate the formation of this structure.

Major types of exoribonucleases

* EC number :

Polynucleotide Phosphorylase (PNPase) Polynucleotide Phosphorylase (PNPase) is a bifunctional enzyme with a phosphorolytic 3' to 5' exoribonuclease activity and a 3'-terminal oligonucleotide polymerase activity. That is, it dismantles the RNA chain starting at the 3' end and working ...

functions as an

exonuclease Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end (exo) of a polynucleotide chain. A hydrolyzing reaction that breaks phosphodiester bonds at either the 3′ or the 5′ end occurs. Its close relative is the ...

as well as a

nucleotidyltransferase Nucleotidyltransferases are transferase enzymes of phosphorus-containing groups, e.g., substituents of nucleotidylic acids or simply nucleoside monophosphates. The general reaction of transferring a nucleoside monophosphate moiety from A to B, can ...

. * EC number : RNase PH functions as an

as well as a

. * EC number 3.1.??:

RNase R RNase R, or Ribonuclease R, is a 3'-->5' exoribonuclease, which belongs to the RNase II superfamily, a group of enzymes that hydrolyze RNA in the 3' - 5' direction. RNase R has been shown to be involved in selective mRNA degradation, particularly o ...

is a close homolog of RNase II, but it can, unlike RNase II, degrade RNA with secondary structures without help of accessory factors. * EC number :

RNase D Ribonuclease (commonly abbreviated RNase) 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 t ...

is involved in the 3'-to-5' processing of pre-

tRNAs Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino a ...

. * EC number 3.1.??:

RNase T Ribonuclease (commonly abbreviated RNase) 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 t ...

is the major contributor for the 3'-to-5' maturation of many stable RNAs. * :

Oligoribonuclease Oligonucleotidase (, ''oligoribonuclease'') is an exoribonuclease derived from '' Flammulina velutipes''. This enzyme catalyses the following chemical reaction A chemical reaction is a process that leads to the chemical transformation of one ...

degrades short oligonucleotides to mononucleotides. * :

Exoribonuclease I 5′-3′ exoribonuclease 1 (Xrn1) is a protein that in humans is encoded by the XRN1 gene. Xrn1 hydrolyses RNA in the 5′ to 3′ direction. Function This gene encodes a member of the 5′-3′ exonuclease family. The encoded protein may b ...

degrades single-stranded RNA from 5'-to-3', exists only in eukaryotes. * :

Exoribonuclease II Exoribonuclease II (, ''ribonuclease II'', ''ribonuclease Q'', ''BN ribonuclease'', ''Escherichia coli exo-RNase II'', ''RNase II'', ''exoribonuclease (misleading)'', ''5'-exoribonuclease'') is an enzyme. This enzyme catalyses the following chemic ...

is a close homolog of Exoribonuclease I.

RNase specificity

The active site looks like a rift valley where all the active site residues create the wall and bottom of the valley. the rift is very thin and the small substrate fits perfectly in the middle of the active site, which allows for perfect interaction with the residues. It actually has a little curvature to the site which the substrate also has. Although usually most exo- and endoribonucleases are not sequence specific, recently

CRISPR CRISPR () (an acronym for clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacte ...

/Cas system natively recognizing and cutting DNA was engineered to cleave ssRNA in a sequence-specific manner.

RNase contamination during RNA extraction

The extraction of RNA in molecular biology experiments is greatly complicated by the presence of ubiquitous and hardy ribonucleases that degrade RNA samples. Certain RNases can be extremely hardy and inactivating them is difficult compared to neutralizing

DNase Deoxyribonuclease (DNase, for short) refers to a group of glycoprotein endonucleases which are enzymes that catalyze the hydrolytic cleavage of phosphodiester linkages in the DNA backbone, thus degrading DNA. The role of the DNase enzyme in cells ...

s. In addition to the cellular RNases that are released, there are several RNases that are present in the environment. RNases have evolved to have many extracellular functions in various organisms. For example, RNase 7, a member of the

superfamily, is secreted by human skin and serves as a potent antipathogen defence. In these secreted RNases, the enzymatic RNase activity may not even be necessary for its new, exapted function. For example, immune RNases act by destabilizing the cell membranes of bacteria.

References

Sources

* D'Alessio G and Riordan JF, eds. (1997) ''Ribonucleases: Structures and Functions'', Academic Press. * Gerdes K, Christensen SK and Lobner-Olesen A (2005). "Prokaryotic toxin-antitoxin stress response loci". ''Nat. Rev. Microbiol.'' (3) 371–382.

External links

IUBMB Enzyme Database for EC 3.1

Integrated Enzyme Database for EC 3.1
{{Portal bar, Biology, border=no EC 3.1 EC 3.1.26 EC 3.1.27