What does DNA 2
Ribonucleic acid is a nucleic acid, i.e. a chain made up of many nucleotides (a so-called polynucleotide). In international and scientific usage, ribonucleic acid is abbreviated to RNA (ribonucleic acid), in the German-speaking area also with RNA.
An essential function of RNA in the cell is the conversion of genetic information into proteins. RNA is involved both as an information carrier (mRNA, RNA viruses) and as a catalytic molecule in the translation of this information into a protein (rRNA, tRNA).
Structure and difference to DNA
In terms of structure, RNA is similar to DNA. In contrast to double-stranded DNA, RNA molecules are usually single-stranded. Both are polynucleotides in which the nucleobases (adenine, guanine, cytosine, uracil or thymine for DNA) on sugars (ribose for RNA; deoxyribose for DNA) are linked to one another via phosphoric acid diesters. Single-strandedness increases the number of possibilities for three-dimensional structures in RNA and allows it to undergo chemical reactions that DNA cannot. In RNA, each nucleotide consists of a ribose (i.e. a pentose: a sugar with five carbon atoms), a phosphate residue and an organic base. The ribose (sugar) of the RNA is identical to that of the DNA, except for a hydroxyl group (instead of a hydrogen atom) at the 2'-position in the pentose ring (hence also Deoxyribonucleic acid D.N / A). This difference makes RNA less stable than DNA, as it enables hydrolysis by bases: the OH group at the 2 'position of the sugar is deprived of its proton by a negatively charged hydroxide ion and the oxygen that remains then forms a ring bond with the Phosphorus, whereby the bond to the next nucleotide is broken. The RNA is broken down into its nucleotides again.
The following organic bases occur in RNA: adenine, guanine, cytosine and uracil. The first three bases are also found in DNA. Uracil, on the other hand, replaces thymine as a complementary base to adenine. RNA presumably uses uracil because it is less energetic to manufacture (no methyl substitution).
Synthesis of RNA
The enzyme RNA polymerase catalyzes the DNA through the process of transcription from nucleoside triphosphate (NTP) the RNA. To do this, the RNA polymerase attaches itself to a DNA sequence called a promoter (transcription initiation). Then it separates the DNA double helix into two single strands of DNA by breaking the hydrogen bonds in a short area. Complementary ribonucleotides are attached to the codogenic strand of DNA through base pairing. With elimination of a pyrophosphate, they are linked to one another by an ester-like bond between phosphoric acid and ribose. The reading direction of the DNA runs from the 3 'end to the 5' end, the synthesis of the complementary RNA accordingly 5 '→ 3'. The opening of the DNA double helix takes place only in a short area, so that the part of the RNA that has already been synthesized hangs out of this opening, with the 5 'end of the RNA first. The synthesis of the RNA is terminated at a terminator sequence. The RNA transcript is then released and the RNA polymerase detaches from the DNA.
RNA molecules can perform different functions. On the one hand, RNA can transmit genetic information. Other RNA molecules help translate this information into proteins and regulate genes. In addition, RNA can also have catalytic functions similar to an enzyme. RNA is therefore given different names, depending on its function. Preceding lower case letters indicate the different types of RNA:
- The mRNA, Messenger RNA (engl. messenger RNA) copies the information contained in a gene on the DNA and carries it to the ribosome, where protein biosynthesis can take place with the help of this information. In each case three nucleotides lying next to one another in the reading frame of the polynucleotide strand form a codon, with the help of which a specific amino acid that is to be incorporated into a protein can be clearly determined. This connection was found in 1961 by Heinrich Matthaei and Marshall Warren Nirenberg. The decoding of the genetic code marks a new beginning in almost all bio-sciences.
- The tRNA, Transfer RNA does not encode any genetic information, but serves as an auxiliary molecule in protein biosynthesis by taking up a single amino acid from the cytoplasm and transporting it to the ribosome. The tRNA is encoded by a specific 'RNA gene'.
- The rRNA, ribosomal RNA, like tRNA, does not carry any genetic information, but is involved in the construction of the ribosome and is also catalytically active in the formation of the peptide bond.
- The hnRNA, heterogeneous nuclear RNA (English heterogeneous nuclear RNA), occurs in the cell nucleus of eukaryotes and is a precursor of the mature mRNA, which is why it is often referred to as pre-mRNA (or pre-mRNA for precursor mRNA).
- The snRNA, small nuclear RNA, in the nucleus of eukaryotes, is responsible for processing the hnRNA in the spliceosome.
- The snoRNA, small nucleolar RNA, are found in the nucleolus, and the closely related scaRNAs in the Cajal bodies.
- The siRNA, small interfering RNA, arises in a signal path of the cell, which is summarized as RNAi (RNA Interference). Here, dsRNA (double-stranded RNA; English double-stranded RNA) is broken up into many smaller fragments of approx. 22 nucleotides in length by the enzyme Dicer (the siRNAs) and incorporated into the enzyme complex RISC (RNA-induced silencing complex). With the help of the incorporated RNA fragments, RISC binds complementarily to DNA, e.g. gene areas, or mRNA and can thus "switch off" them. siRNAs are currently (2006) intensively researched for their involvement in various cell processes and diseases.
- The microRNAs are closely related to siRNAs and are used to regulate cellular processes such as proliferation and cell death.
- The aRNA, antisense RNA, is used to regulate gene expression.
- The Riboswitches serve for gene regulation. They can have either an activating or a repressive effect.
- The Ribozymes are catalytically active RNA molecules. Like enzymes, they catalyze chemical reactions.
In the majority of living beings, RNA plays a subordinate role to DNA as an information carrier: Here, DNA is the permanent storage medium for genetic information, while RNA serves as a temporary store. Only RNA viruses (the majority of all viruses) use RNA instead of DNA as a permanent storage medium. A distinction is made between the following types of RNA for the taxonomy of viruses:
- dsRNA: Double stranded RNA
- ss (+) RNA: Single-stranded RNA used as mRNA.
- ss (-) RNA: Single-stranded RNA that serves as a template for mRNA production
In addition, some viruses use RNA as a replication intermediate (e.g. retroviruses and hepadnaviruses)
Breakdown of RNA
Since new RNA is constantly being formed and since different transcripts are required at different times (differential gene expression), the RNA in the cell must not be too stable, but must also be subject to degradation. This is done with the help of RNases, enzymes that separate the connections of the sugar structure of the RNA and thus form the monomers (or oligomers) which can be used again to form new RNA. When an RNA is to be degraded is mainly (but not exclusively) determined by the length of the poly-A tail, which is gradually shortened as the RNA remains in the cytoplasm. If the length of this tail falls below a critical value, the RNA is quickly degraded. In addition, the RNAs can contain stabilizing or destabilizing elements that enable further regulation.
At least in the case of the mRNA from eukaryotes, the RNA breakdown does not take place somewhere in the cytoplasm, but in the so-called "P-Bodies" (processing bodies), which are very rich in RNAses and other enzymes involved in the RNA turnover (breakdown). Together with "stress granules", these bodies continue to serve for the short-term storage of mRNA and thus again demonstrate the close connection of the RNA metabolism (here translation and RNA degradation).
The RNA World Hypothesis
The RNA world hypothesis was first proposed by Walter Gilbert in 1986 and states that RNA molecules were the precursors of organisms in chemical evolution.
The hypothesis can be derived from the ability of RNA to store, transfer and reproduce genetic information and from its ability to catalyze reactions as ribozymes. In an evolutionary environment, those RNA molecules would occur more frequently that preferentially reproduce themselves.
The starting point are simple self-replicating RNA molecules. Some of them acquire the property of catalyzing the synthesis of proteins, which in turn catalyze the synthesis of RNA and their own synthesis (development of translation). Some RNA molecules assemble into double-stranded RNA molecules that develop into DNA molecules and carriers of genetic information (development of transcription).
Certain RNA molecules serve as the basis, which can generate copies of any RNA template and thus of themselves. Jennifer A. Doudna and Jack W. Szostak used the self-splicing intron of the eukaryotic unicellular cell as a template for developing this type of RNA Tetrahymena thermophila. There is thus the possibility that the actually catalytic molecules in the ribosomes are the rRNA and thus that RNA catalyzes protein synthesis. However, there are limitations in that self-replicating RNA does not require mononucleotides as building blocks, but oligonucleotides and auxiliary substances.
In 2001 it was discovered that the important catalytic centers of the ribosomes are provided by RNA and not, as previously assumed, proteins. This shows that a catalytic function of RNA, as proposed in the RNA world hypothesis, is now used by living things. Since ribosomes are considered to be the very original building blocks of cells, this discovery is considered to be an important contribution to the underpinning of the RNA world hypothesis. It is now certain that RNA molecules - at least in principle - are able to chain amino acids to proteins. In this context is also the PNA (Peptide nucleic acid) as a possible precursor of the RNA of interest.
See also: Quasi-species, Manfred Eigen
Several Nobel Prizes have already been awarded for research on RNA. As early as 1959, S. Ochoa and A. Kornberg received the Nobel Prize in Medicine for their studies on the synthesis of RNA by RNA polymerases. For their discovery of the catalytic activity of RNA molecules (see ribozyme), S. Altman and T. Cech were honored with the 1989 Nobel Prize in Chemistry. Finally, in 1993, R. Roberts and P. Sharp received the Nobel Prize for Medicine for their studies on the processing of RNA in eukaryotes (see also Splicing). And last but not least, Andrew Fire and Craig Mello received the Nobel Prize in Medicine in 2006 for the discovery of RNA interference, and almost at the same time Roger Kornberg (the son of the previous awardee A. Kornberg) was honored for his studies on RNA polymerase.
- J. Marx: P-Bodies Mark the Spot for Controlling Protein Production. Science 2005; 4 Vol. 310. no. 5749, pp. 764 - 765 (summary )
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