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