RNA: Definition and Much More from Answers.com
- ️Wed Jul 01 2015
Ribonucleic acid (RNA) molecules, which are linear chains (or polymers) of ribonucleotides, perform a number of critical functions. Many of these functions are related to protein synthesis. Some RNA molecules bring genetic information from a cell's chromosomes to its ribosomes, where proteins are assembled. Others help ribosomes translate genetic information to assemble specific sequences of amino acids.
Molecular Structure
Ribonucleotides, the building blocks of RNA, are molecules that consist of a nitrogen-containing base, a phosphate group, and ribose, a five-carbon sugar. The nitrogen-containing base may be adenine, cytosine, guanine, or uracil. These four bases are abbreviated as A, C, G, and U.
RNA is similar to deoxyribonucleic acid (DNA), another class of nucleic acid. However, DNA nucleotides contain deoxyribose, not ribose, and they use the nitrogen-containing base thymine (T), not uracil, along with ade-nine, cytosine, and guanine.
The nucleotides in DNA and RNA molecules are linked together to form chains. The link between two nucleotides is between a phosphate group attached to the fifth (5′ or "five prime") carbon of the sugar on one nucleotide and a hydroxyl group on the third (3′ or "three prime") carbon of the sugar on the other. The link is called a 5′-3′ phosphodiester bond.
RNA, therefore, can be described as a chain of ribose sugars linked together by phosphodiester bonds, with a base protruding from each sugar, as shown in the figure below. The 5′-3′ linkage gives RNA directionality, or polarity, and results in its having two ends with different chemical structures. The 5′ end usually has one or three free phosphate groups, and the 3′ end usually has a free hydroxyl group.
Whereas DNA is usually double-stranded, with the bases on one strand pairing up with those on the other, RNA usually exists as single chains of nucleotides. The bases in RNA do, however, follow Watson-Crick base-pair rules: A and U can pair with each other, as can G and C. There is usually extensive pairing of bases within a single strand of RNA.
RNA strands fold, with the bases in one part of the strand pairing with the bases in another. Folding can create both "secondary" and "tertiary" structures. Secondary structures are those that can be described in two dimensions and that can be thought of as simple loops or helices. Tertiary structures are complex, three-dimensional shapes.
The most common secondary structures, "hairpins," "loops," and "pseudo-knots," are shown in the figure below. Such secondary structures are formed when hydrogen bonds form between bases in the nucleotides and by the stacking of bases to form helical structures.
Tertiary structures usually involve interactions between nucleotides that are distant from each other along an RNA strand. Such interactions may arise from hydrogen bonding between bases, as in regular Watson-Crick base pairing, or from interactions among other chemical groups in the nucleotides. Some RNA molecules, such as ribosomal RNA (rRNA) and transfer RNA (tRNA), have structures that are very complex. In structure they resemble proteins more than they do DNA.
To understand the function of a given RNA molecule, scientists often need to know its structure. There are three general strategies for analyzing RNA structure. First, using the relatively simple base-pairing rules for RNA and the basic principles of thermodynamics, computers can be used to predict secondary RNA structure, although not always with complete success.
Second, researchers can analyze RNA molecules from various organisms and compare those molecules that have the same function. Even when the nucleotide sequences vary between species, important structures are usually preserved.
Third, the structure of an RNA molecule can be determined experimentally, using enzymes to cut it or chemicals to modify it. Some enzymes and chemicals cut or modify only nonpaired, single-stranded portions of the RNA molecule, allowing researchers to identify double-stranded regions by examining which ones remain uncut and unmodified.
Despite the usefulness of each of these methods, none can provide a complete and accurate three-dimensional structure. A more complete determination of structure can be achieved by the biophysical methods of X-ray crystallography and nuclear magnetic resonance.
Synthesis
RNA molecules are synthesized by enzymes known as RNA polymerases in a process called transcription. Usually, one strand of a double-stranded DNA molecule is used as a template for the RNA. The order of ribonucleotides that are assembled to form the RNA molecule is determined by the order of the deoxyribonucleotides in the DNA strand. The genetic information in the DNA sequence is thus reproduced in the RNA molecule. Sometimes, but rarely, an RNA molecule is synthesized using another RNA molecule as the template.
Often, when RNA molecules are synthesized, they are in a form that prevents them from carrying out their function. To become functional, they must undergo processing, which can involve removing segments of the strands or modifying specific nucleotides. The link between a base and a ribose may be altered, or extra chemical groups may be added to the bases or ribose molecules. Many RNA molecules are associated with proteins during or after their synthesis. Together, the RNA and protein are referred to as RNA-protein particles (RNPs).
In eukaryotes, RNA that is encoded by nuclear chromosomes is synthesized in the nucleus. The processing and assembly of many small RNA molecules in higher eukaryotes is accomplished in Cajal bodies, which are coiled structures in the nucleus that were identified more than 100 years ago but that have begun to be investigated in detail only recently. The synthesis of those RNA molecules that are components of ribosomes occurs in the nucleolus, a part of the nucleus. RNA synthesis and processing also occurs in the mitochondria and chloroplasts, when the RNA will be used in those organelles.
After being processed and assembled, RNPs either remain in the nucleus or are exported to the cytoplasm through the nuclear pores. Some are also exported and modified in the cytoplasm and then imported back into the nucleus. In prokaryotes, where there is no nucleus, the synthesis and processing of RNA, as well as the assembly of RNPs, occurs in the cytoplasm.
Function
Almost all types of RNA play a role in translation, which is the process of protein synthesis. Translation requires three types of RNA: messenger RNA (mRNA), which ranges in length from a few hundred to many thousands of nucleotides; tRNA, which is 75 to 85 nucleotides long; and rRNA, which is 1,500 to 4,000 nucleotides long.
Molecules of mRNA, each of which contains a copy of at least one gene, are the intermediates between DNA and protein. These mRNA molecules bring the genetic code from the DNA, which is in the nucleus, to ribosomes, which are in the cytoplasm. They attach to the ribosomes and determine the order in which amino acids are assembled to synthesize a protein. Of the three types of RNA required for translation, mRNA molecules have the simplest structure.
Next, tRNA molecules function as adapters that help translate the nucleotide sequences in mRNA into amino acid sequences, so specific proteins can be constructed. There are many different types of tRNA, each of which is capable of binding to one of the twenty amino acids that are the building blocks of proteins.
Finally, rRNA molecules, which account for most of a ribosome's mass, are, according to recent experiments, the part of the ribosome responsible for linking amino acids into a growing protein chain. Ribosomes, the organelles that assemble a particular sequence of amino acids to form proteins, contain three or four different molecules of rRNA, along with at least fifty different proteins.
Both rRNA and tRNA are stable forms of RNA that last through several cell divisions. In contrast, mRNA is normally unstable, with a lifetime that can be as short as a few minutes. This instability has probably evolved because it lets cells quickly stop synthesizing proteins that are no longer needed. In some cases, enzymes called ribonucleases (RNases) actively degrade certain mRNA molecules. For example, mRNA that encodes a particular protein regulating the cell cycle is degraded when the protein has carried out its function.
In certain cells, mRNA can exist in a stable form for decades. When egg cells are formed, for example, some of the mRNA in the cells is associated with "storage proteins" and lasts until after the eggs are fertilized. During embryonic development, this maternal mRNA becomes activated for translation and associates with translating ribosomes. It usually decays after it has been used to produce a certain amount of protein.
Less Common Types of Rna
Several types of less abundant, small RNA molecules perform essential functions in both the nucleus and the cytoplasm. All organisms contain cytoplasmic RNPs that are involved in exporting proteins from cells. During the synthesis of proteins that are destined to be exported, the ribosome and mRNA associate with an "export-RNP," which helps them dock at an export pore in the cell membrane. As it formed, the protein is threaded through the membrane to the outside of the cell. In eukaryotes, this same strategy is used to transport proteins into the endoplasmic reticulum, where some newly synthesized proteins are sorted and modified.
RNase P is another RNP found in all forms of life. This RNA-containing enzyme helps turn precursor tRNA into mature tRNA molecules. It does so by cleaving a section off the 5′ end of the precursor molecules.
Small nucleolar RNAs, which are known as snoRNAs and which are found in the nucleoli of eukaryotes and in Archaea, are required for the processing of precursor rRNA. During the assembly of new ribosomes, snoRNAs help remove regions of the precursor molecules and modify specific nucleotides.
Often, mRNA molecules in eukaryotes and in Archaea contain sequences that do not code for amino acids. These sequences, called introns, must be spliced out before translation begins. In eukaryotes, small nuclear RNAs (snRNAs) in the nucleus remove these introns. Once the introns are removed, the mature mRNA molecules are exported, through nuclear pores, into the cytoplasm, where they associate with ribosomes for translation.
Some viral genomes consist of single-stranded or double-stranded RNA, not DNA. Examples are found among both prokaryotic and eukaryotic viruses and include HIV, as well as viruses causing some forms of cancer.
Bibliography
Lodish, Harvey, et al. Molecular Cell Biology, 4th ed. New York: W. H. Freeman, 2000.
Meili, M., B. Albert-Fournier, and M. C. Maurel. "Recent Findings in the Modern RNA World." International Microbiology 4 (2001): 5-11.
Robinson, Richard. Biology. Farmington Hills, MI: Macmillan Reference USA, 2002.
Storz, G. "An Expanding Universe of Non-coding RNAs." Science 296 (2002): 1260-1263.
—Lasse Lindahl
- For other uses, see RNA (disambiguation).
Left: An RNA strand, with its nitrogenous bases. Right: Double-stranded DNA.
Ribonucleic acid or RNA is a nucleic acid polymer consisting of nucleotide monomers, which plays several important roles in the processes of translating genetic information from deoxyribonucleic acid (DNA) into proteins. 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.
DNA stands for deoxyribonucleic acid, while RNA stands for ribonucleic acid. RNA is very similar to DNA, but differs in a few important structural details: RNA is usually single stranded, while DNA is usually double stranded. RNA nucleotides contain ribose sugars while DNA contains deoxyribose, and RNA uses the nucleotide uracil in its composition, instead of thymine which is 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[citation needed]) 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 nucleotide 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. 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.
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). 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.
The most important structural feature of RNA, 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 deoxyribose, RNA contains ribose, (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 complementary nucleotide to 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 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)
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 do not have 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)
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)
Ribosomal RNA is the catalytic component of the ribosomes, the protein synthesis 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
RNA genes (sometimes referred to as non-coding RNA or small RNA) are genes that encode RNA which 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
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
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 energy 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
- ^ Fiers W et al., Complete nucleotide-sequence of bacteriophage MS2-RNA - primary and secondary structure of replicase gene, Nature, 260, 500-507, 1976
- ^ Rassoulzadegan M., et al. Nature, doi:10.1038/nature04674 , 2006
- ^ 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
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