(Redirected from DsRNA):''For other uses, see
RNA (disambiguation).''
'Ribonucleic acid' or 'RNA' is a
nucleic acid polymer consisting of
nucleotide monomers that plays several important roles in the processes that translate genetic information from deoxyribonucleic acid (
DNA) into
protein products; RNA acts as a messenger between DNA and the protein synthesis complexes known as
ribosomes, forms vital portions of ribosomes, and acts as an essential carrier molecule for
amino acids to be used in protein synthesis.
RNA is very similar to DNA, but differs in a few important structural details: RNA nucleotides contain
ribose sugars while DNA contains
deoxyribose and RNA uses predominantly
uracil instead of
thymine present in DNA. RNA is
transcribed from DNA by
enzymes called
RNA polymerases and further processed by other enzymes. RNA serves as the template for translation of genes into
proteins, transferring
amino acids to the
ribosome to form proteins, and also translating the transcript into proteins.
Nucleic acids were discovered in 1868 (some sources indicate 1869) by
Johann Friedrich Miescher (1844-1895), who called the material 'nuclein' since it was found in the nucleus. It was later discovered that prokaryotic cells, which do not have a nucleus, also contain nucleic acids. The role of RNA in protein synthesis had been suspected since 1939, based on experiments carried out by
Torbjörn Caspersson,
Jean Brachet and
Jack Schultz.
Hubert Chantrenne elucidated the messenger role played by RNA in the synthesis of
proteins in
ribosome.Finally,
Severo Ochoa discovered the RNA, winning Ochoa the 1959
Nobel Prize for Medicine. The sequence of the 77 nucleotides of a yeast RNA was found by
Robert W. Holley in 1964, winning Holley the 1968
Nobel Prize for Medicine. In
1976,
Walter Fiers and his team at the
University of Ghent determined the complete nucleotide sequence of
bacteriophage MS2-RNA.
[1]
Chemical and Stereochemical structure
RNA is a polymer with a ribose and
phosphate backbone and four different bases:
adenine,
guanine,
cytosine, and
uracil. The first three are the same as those found in DNA, but in RNA
thymine is replaced by uracil as the base complementary to adenine. This base is also a pyrimidine and is very similar to thymine. Uracil is energetically less expensive to produce than thymine, which may account for its use in RNA. In DNA, however, uracil is readily produced by chemical degradation of cytosine, so having thymine as the normal base makes detection and repair of such incipient mutations more efficient. Thus, uracil is appropriate for RNA, where quantity is important but lifespan is not, whereas thymine is appropriate for DNA where maintaining sequence with high fidelity is more critical.
However, there are also numerous modified bases and sugars found in RNA that serve many different roles.
Pseudouridine (Ψ), in which the linkage between uracil and ribose is changed from a C–N bond to a C–C bond, and ribothymidine (T), are found in various places (most notably in the TΨC loop of
tRNA). Thus, it is not technically correct to say that uracil is found in RNA in place of thymine. Another notable modified base is hypoxanthine (a deaminated Guanine base whose nucleoside is called
Inosine). Inosine plays a key role in the Wobble Hypothesis of the
Genetic Code. There are nearly 100 other naturally occurring modified nucleosides, of which pseudouridine and nucleosides with 2'-O-methylribose are by far the most common. The specific roles of many of these modifications in RNA are not fully understood. However, it is notable that in ribosomal RNA, many of the post-translational modifications occur in highly functional regions, such as the peptidyl transferase center and the subunit interface, implying that they are important for normal function.
Single stranded RNA exhibits a right handed stacking pattern that is stabilized by base
stacking. [reference?]
The most important structural feature of RNA, indeed the only consistent difference between the two nucleic acids, that distinguishes it from DNA is the presence of a
hydroxyl group at the 2'-position of the ribose sugar. The presence of this functional group enforces the C3'-endo sugar conformation (as opposed to the C2'-endo conformation of the deoxyribose sugar in DNA) that causes the helix to adopt the A-form geometry rather than the B-form most commonly observed in DNA. This results in a very deep and narrow major groove and a shallow and wide minor groove. A second consequence of the presence of the 2'-hydroxyl group is that in conformationally flexible regions of an RNA molecule (that is, not involved in formation of a double helix), it can chemically attack the adjacent phosphodiester bond to cleave the backbone.
Comparison with DNA
RNA and
DNA differ in three main ways. First, unlike DNA which is double-stranded, RNA is a single-stranded molecule in most of its biological roles and has a much shorter chain of nucleotides. Secondly, while DNA contains ''deoxyribonucleic acid'', RNA contains ''ribonucleic acid'', (there is no hydroxyl group attached to the pentose ring in the
2' position in DNA, whereas RNA has two hydroxyl groups). These hydroxyl groups make RNA less stable than DNA because it is more prone to
hydrolysis. In light of this, several types of RNA (tRNA, rRNA) contain a great deal of secondary structure, which help promote stability. Thirdly, the base-pair of
adenine is not
thymine, as it is in DNA, but rather
uracil, which is an
unmethylated form of thymine.
Like DNA, most biologically active RNAs including tRNA, rRNA, snRNAs and other non-coding RNAs (such as the SRP RNAs) are extensively base paired to form double stranded helices. Structural analysis of these RNAs have revealed that they are not, "single-stranded" but rather highly structured. Unlike DNA, this structure is not just limited to long double-stranded helices but rather collections of short helices packed together into structures akin to proteins. In this fashion, RNAs can achieve chemical
catalysis, like enzymes. For instance, determination of the structure of the ribosome in 2000 revealed that the active site of this enzyme that catalyzes peptide bond formation is composed entirely of RNA.
Synthesis
Synthesis of RNA is usually catalyzed by an enzyme -
RNA polymerase, using
DNA as a template. Initiation of synthesis begins with the binding of the enzyme to a
promoter sequence in the DNA (usually found "upstream" of a gene). The DNA double helix is unwound by the
helicase activity of the enzyme. The enzyme then progresses along the template strand in the 3’ -> 5’ direction, synthesizing a complementary RNA molecule with elongation occurring in the 5’ -> 3’ direction. The DNA sequence also dictates where termination of RNA synthesis will occur.
There are also a number of RNA-dependent RNA polymerases as well that use RNA as their template for synthesis of a new strand of RNA. For instance, a number of RNA viruses (such as poliovirus) use this type of enzyme to replicate their genetic material. Also, it is known that RNA-dependent RNA polymerases are required for the RNA interference pathway in many organisms.
Biological roles
Messenger RNA (mRNA)
Main articles: Messenger RNA
Messenger RNA is RNA that carries information from
DNA to the
ribosome sites of protein synthesis in the cell. In eukaryotic cells, once mRNA has been transcribed from DNA, it is "processed" before being exported from the nucleus into the cytoplasm, where it is bound to
ribosomes and translated into its corresponding protein form with the help of
tRNA. In prokaryotic cells, which have not partition into nucleus and cytoplasm compartments, mRNA can bind to ribosomes while it is being transcribed from DNA. After a certain amount of time the message degrades into its component nucleotides, usually with the assistance of ribonucleases.
Transfer RNA (tRNA)
Main articles: Transfer RNA
Transfer RNA is a small RNA chain of about 74-95
nucleotides that transfers a specific
amino acid to a growing
polypeptide chain at the
ribosomal site of
protein synthesis during
translation. It has sites for
amino-acid attachment and an
anticodon region for
codon recognition that binds to a specific sequence on the
messenger RNA chain through hydrogen bonding. It is a type of
non-coding RNA.
Ribosomal RNA (rRNA)
Main articles: Ribosomal RNA
'Ribosomal RNA' is the catalytic component of the
ribosomes, the protein synthetic factories in the cell.
Eukaryotic ribosomes contain four different rRNA molecules: 18S, 5.8S, 28S, and 5S rRNA. Three of the rRNA molecules are synthesized in the
nucleolus, and one is synthesized elsewhere. rRNA molecules are extremely abundant and make up at least 80% of the RNA molecules found in a typical
eukaryotic cell.
In the cytoplasm, ribosomal RNA and protein combine to form a nucleoprotein called a ribosome. The ribosome binds mRNA and carries out protein synthesis. Several ribosomes may be attached to a single mRNA at any time.
Non-coding RNA
Main articles: Non-coding RNA
RNA genes (sometimes referred to as non-coding RNA or small RNA) are genes that encode RNA that is not
translated into a protein. The most prominent examples of RNA genes are
transfer RNA (tRNA) and
ribosomal RNA (rRNA), both of which are involved in the process of translation. However, since the late
1990s, many new RNA genes have been found, and thus RNA genes may play a much more significant role than previously thought.
In the late 1990s and early 2000, there has been persistent evidence of more complex transcription occurring in
mammalian cells (and possibly others). This could point towards a more widespread use of RNA in biology, particularly in
gene regulation. A particular class of non-coding RNA,
micro RNA, has been found in many metazoans (from ''
Caenorhabditis elegans'' to ''
Homo sapiens'') and clearly plays an important role in regulating other genes.
First proposed in 2004 by Rassoulzadegan and published in Nature 2006,
[2] RNA is implicated as being part of the
germline. If confirmed, this result would significantly alter the present understanding of genetics and lead to many questions on DNA-RNA roles and interactions.
Catalytic RNA
Main articles: Ribozyme
Although RNA contains only four bases, in comparison to the twenty-odd amino acids commonly found in proteins, certain RNAs are still able to catalyse chemical reactions. These include cutting and
ligating other RNA molecules and also the catalysis of
peptide bond formation in the
ribosome.
Double-stranded RNA
Double-stranded RNA (or dsRNA) is RNA with two complementary strands, similar to the DNA found in all "higher" cells. dsRNA forms the genetic material of some
viruses. In eukaryotes, it acts as a trigger to initiate the process of
RNA interference and is present as an intermediate step in the formation of
siRNAs (small interfering RNAs).
siRNAs are often confused with
miRNAs;
siRNAs are double-stranded, whereas
miRNAs are single-stranded. Although initially single stranded there are regions of intra-molecular association causing hairpin structures in pre-miRNAs; immature miRNAs. Very recently, dsRNA has been found to induce gene expression at transcriptional level, a phenomenon named "small RNA induced gene activation
RNAa". Such dsRNA is called "small activating RNA (saRNA)".
RNA world hypothesis
Main articles: RNA world hypothesis
The RNA world hypothesis proposes that the earliest forms of life relied on RNA both to carry genetic information (like DNA does now) and to catalyze biochemical reactions
like an enzyme. According to this hypothesis, descendants of these early lifeforms gradually integrated DNA and proteins into their metabolism.
RNA secondary structures
The functional form of single stranded RNA molecules (like
proteins) frequently requires a specific tertiary structure. The scaffold for this structure is provided by secondary structural elements which are hydrogen bonds within the molecule. This leads to several recognizable "domains" of secondary structure like hairpin loops, bulges and internal loops. The secondary structure of RNA molecules can be predicted computationally by calculating the minimum free energies (MFE) structure for all different combinations of hydrogen bondings and domains. There has been a significant amount of research directed at the
RNA structure prediction problem.
Online tools for MFE structure prediction from single sequences are provided by
MFOLD and
RNAfold.
XNAfold is a Window-based program adopted the fold routines and enery parameters from the RNAfold library. A direct comparison of RNA secondary structures predicted by free energy minimisation with those derived from experimentally determined three dimensional structures was carried out to assess the prediction accuracy of XNAfold. Based on analysis of 133 different RNA sequences from the Protein Data Bank, the accuracy of secondary structure prediction was 84%. The
minimum free energy structure predicted was identical to the experimentally determined structure in 58% of cases. Additionally, the experimentally determined structures matched one of the sub-optimal structures computed in 26% of cases
[3].
Comparative studies of conserved RNA structures are significantly more accurate and provide evolutionary information. Computationally reasonable and accurate online tools for alignment folding are provided by
KNetFold,
RNAalifold and
Pfold.
A package of RNA structure prediction programs is also available for Windows:
RNAstructure.
A database of RNA sequences and secondary structures is available from
Rfam, analyses and links to RNA analysis tools are available from
Wikiomics.
References
1. Fiers W et al., Complete nucleotide-sequence of bacteriophage MS2-RNA - primary and secondary structure of replicase gene, Nature, 260, 500-507, 1976
2. Rassoulzadegan M., et al. Nature, doi:10.1038/nature04674 , 2006
3. Zou Y., Reliability of RNA secondary structure prediction with XNAfold, Online Journal of Bioinformatics, 5, 49-58, 2004
External links
★
RNA World website
★
Nucleic Acid Database Images of DNA, RNA and complexes.
See also
★
Antisense mRNA
★
Dot plot (bioinformatics)
★
Genetics
★
Molecular biology
★
RNAa
★
RNA interference (RNAi)
★
RNA Ontology Consortium
★
RNA world hypothesis
★
Severo Ochoa
★
Sequence profiling tool
★
Phosphoramidite
★
Quantification of nucleic acids
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