Ribonuclease

( RNases also written erroneously ) Ribonucleases, short RNases are enzymes that catalyze the hydrolytic cleavage of phosphodiester bonds in ribonucleic acid (RNA ) chains. This reaction is part of the processing and degradation of RNA. RNases are present in all organisms and constitute an indispensable component of cellular metabolism. In humans, about 50 RNases are known which consist partly of several subunits (protein complexes); nine human RNases are currently associated with rare genetic diseases.

RNases are among the nucleases. Their classification is on the point and the reaction product. Serves the split in the middle of the RNA chain is endoribonucleases while exoribonucleases act on the for they each specific end of the RNA chains. It can 5'- phosphomonoester or other incurred thereby. Thus, the Commission of the IUBMB enzyme, the enzyme Categories 3.1.26 -. 3.1.27 and -. Endonucleases and for 3.1.13 -. 3.1.14 and -. Reserved for exonucleases, while nucleases that can degrade both RNA and DNA ( 3.1.15 -. 3.1.16 and -. ) are hardly known examples. It may be single-stranded or double-stranded RNA, this criterion is not suitable for distinguishing the RNases.

4.1 RNase R
4.2 RNase D

Function

The RNases are a diverse group of enzymes, all of which cut the chain molecule RNA by separating a phosphate ester bond to the ribose. First, they differ in whether they attack single-or double-stranded RNA or RNA / DNA hybrids. The function can be non-specific or be limited to the location of certain nucleotides or nucleotide sequences. Recycling is an important but not the only purpose. For example, the life of tRNA must be limited so that protein synthesis can be controlled by the means of gene regulation. RNases also interact with during the processing of the cell 's own RNA ( tRNA and rRNA iw ). In addition, RNases can destroy the genome of RNA viruses penetrated and thus take part in the innate immune response. Ribonucleases can be inhibited with diethyl dicarbonate.

Pathology

Of nine RNases of human polymorphisms are known, which can lead to rare genetic diseases.

Endoribonucleases

RNase A

The RNase A cleaves single-stranded RNA. It detects the two pyrimidines U and C and cleaves the phosphodiester bond at the 5 ' position of the ribose of RNA in each case in the chain following U or C nucleotide. RNase A can be found among others in sweat. Thus they also degrades RNA viruses that could infect the body. Thus, the secretion of RNase A belongs to the welding to the defense mechanisms of the body. This secretion leads to RNase A is a very frequently occurring extracellularly "Environmental nuclease ".

A striking property of a protein is the high heat stability: RNase A can withstand cooking (that is, 100 ° C) without denaturing. She is a frequently used laboratory reagent. Ribonuclease A was one of the first biomolecules, whose structure was elucidated. In 1967 this was achieved, two teams independently.

RNase H

RNase H is a non-specific endoribonuclease that recognizes RNA: DNA heteroduplexes and the RNA component removed. The cleavage of the RNA via a hydrolytic enzyme-bound divalent metal ion. They met, inter alia, an important function in the replication of DNA by removing the annealed RNA primer again. There are two sub-types. RNase H1 is monomeric and binds to 2'OH groups of four consecutive ribonucleotides. Again consist of two isoforms, a nuclear isoform whose function is unknown, and a mitochondrial isoform, which is necessary for replication of the mitochondrial DNA of RNase H1. RNase H2 consists of three proteins, RNASEH2A, RNASEH2B RNASEH2C and which form a trimeric complex, wherein the catalytic site is located in the protein RNASEH2A.

RNase H2 removed replication erroneously incorporated into the DNA of RNA - monomers, which are then replaced with the correct DNA monomers. In replication, the corresponding ribonucleotides are in fact installed instead of the correct deoxyribonucleotides ° with a frequency of one to several thousand. The repair is necessary because RNA is far more susceptible to spontaneous hydrolysis than DNA.

In case of insufficient enzyme activity, such as by mutations in one of the three protein genes, it is due to the then remaining ribonucleotides on a genome instability through to strand breakage and accumulation of DNA segments. This can disrupt the cell cycle and lead to apoptosis via activation of the p53 signaling pathway. The accumulated DNA segments can then cause inflammation of the innate immune response, which corresponds to the pathogenesis of Aicardi - Goutières syndrome, in which mutations are frequently one of the three RNase H2 genes in fact. If there is no RNASEH2B in the knockout mouse, this leads to early embryonic lethality during gastrulation already ..

RNase P

RNase P is a ribozyme, i.e., In contrast to the vast majority of enzymes, it is not a protein but itself consists of RNA. Their function is to cleave a precursor sequence in the processing of tRNA.

Exoribonucleases

RNase R

RNase R is a 3 '→ 5' exoribonuclease, which is involved in the degradation of mRNA in bacteria.

RNase D

RNase D is a 3 '→ 5' exoribonuclease, which is involved in the processing of the tRNA.