RNA/Protein Translation

FIELDS OF STUDY: Biochemistry; Genetics; Molecular Biology

ABSTRACT

The process by which RNA translates protein structures from the genetic code in the DNA molecule is described. The process is controlled by a simple series of three-nucleotide units called codons that determine which amino acids are to be assembled in which order to create every protein and enzyme in the entire biological system.

The Protein Assembly Line

Translation of the primary structure of a protein from the genetic code in the deoxyribonucleic acid (DNA) molecule is a kind of assembly-line manufacturing process that takes place in all biological systems. In essence, ribonucleic acid (RNA) reads the blueprint and assembly instructions from the DNA molecule, delivers the necessary parts to the "assembly line" in the ribosome complex, and assembles the parts into proteins according to the design specified by the DNA molecule.

The process is, of course, more complicated than that, as it is the result of many different enzyme-mediated chemical reactions that must occur in the proper sequence for each one of the many thousands of different proteins that are synthesized in the routine functioning of a living cell. The DNA molecule itself is composed of very few molecular components, but it is nevertheless subject to modification due to any number of causes. Each modification or perturbation of the normal structure of the DNA molecule has effects that are reflected in the cell’s ability to produce the correct proteins for its proper functioning. A mutation of the DNA structure may prevent the production of a necessary protein, or it may cause the production of proteins that are at best unusable and at worst dangerous. Mutations that cause the normal process that halts protein synthesis to be disrupted can result in the formation of cancerous growths. Most often, however, the complexity of the process serves to prevent problems by simply shutting down the process when any aberration in the DNA structure is encountered.

Transcription and Translation

The structure of the DNA molecule consists of a very long backbone of deoxyribose sugar molecules alternating with phosphate groups. To each deoxyribose sugar molecule is attached one of four base molecules called nucleotides: adenine, cytosine, guanine, or thymine (commonly abbreviated A, C, G, and T). A second, equally long strand of DNA has a complementary structure to the first. When the two strands combine in the duplex DNA molecule to form its characteristic double-helix structure, the bases coordinate to each other, so that each instance of adenine or cytosine in one strand matches to thymine or guanine, respectively, in the other strand. The exact matching of the bases along the entire length of the two strands is required for the formation of the duplex DNA molecule.

To begin the transcription process—the process of copying a segment of DNA onto a segment of RNA—enzymes specific to the process attach to the DNA molecule and temporarily separate the two strands. This exposes the sequence of bases in the nucleotides of the DNA strand and begins the process of gene expression. Other enzymes called RNA polymerases then assemble free nucleotides to match the exposed sequence of DNA nucleotide bases. The strand that the RNA attaches to is called the template or noncoding strand, while the other strand, to which the template strand was originally attached, is called the coding strand. Because nucleotides always coordinate to their complementary bases, the sequence of the RNA strand will be identical to that of the DNA coding strand, with one difference: in RNA, the base uracil (U), rather than thymine, is used to complement adenine. Thus, a thymine base in the coding strand will coordinate to an adenine base in the template strand, which will in turn produce a uracil base in the RNA strand.

The formation of this new RNA strand is initiated and terminated by specific sequences of nucleotide bases on the DNA strand. When the "stop" sequence is encountered, the assembly process ends, and another enzyme separates the complementary RNA strand from the DNA strand, releasing it into the cytosol (intracellular fluid) of the cell as a molecule of messenger RNA (mRNA). At this point, transcription is complete and translation begins.

In the cytosol, the molecule of mRNA connects to ribosome complexes, which are themselves composed of another type of RNA called ribosomal RNA (rRNA). The binding of the mRNA to the rRNA occurs by matching nucleotide base sequences in the two strands. This exposes specific three-unit sequences of the mRNA termed codons, which identify the specific amino acid that is to be added onto the protein molecule being assembled at that location.

A third form of RNA, called transfer RNA (tRNA), transports particular amino acids to the site designated by the codon on the mRNA. Each tRNA molecule has a matching anticodon segment in its primary structure that attaches to the codon in the mRNA strand. In this way, amino acids are brought into the ribosome complex in the sequence that had been specified in the nucleotide sequence of the parent DNA molecule.

As each amino acid is brought into the ribosome complex by tRNA, the enzymes in the ribosome catalyze the formation of peptide bonds between the amino acids in the sequence. The resulting string of amino acids is called a polypeptide. After the polypeptide structure is released from the ribosome complex, it undergoes a process known as protein folding, through which it assumes the secondary structural features that characterize it as a protein or an enzyme. With the release of the new protein molecule, the process of translation is complete.

Overlapping of Sequences in mRNA

Each codon of the mRNA strand consists of three nucleotides, and merely shifting over one nucleotide in the sequence creates a new set of three nucleotides and therefore a new codon. For example, the DNA nucleotide series CCTACCTGG codes for the amino acids proline, threonine, and tryptophan. Shifting over two nucleotides creates the sequence TACCTGG, which codes for the amino acids tyrosine and leucine in an entirely different polypeptide chain. Viruses use this codon shifting to generate the various proteins required for their successful infection of a host cell.

The Genetic Code and the Human Genome

The discovery of the molecular structure of DNA in 1943 enabled research that ultimately revealed the genetic code. Through numerous experimental studies that included the use of synthetic nucleotide sequences, researchers were eventually able to identify which groups of nucleotides were codons for which amino acids. Since the number of three-nucleotide combinations that can be formed with four nucleotides (sixty-four) is much greater than the twenty essential amino acids used in protein synthesis, there is significant redundancy in the genetic code, with several different codons specifying the same amino acid. The human genome was finally deciphered at the end of the twentieth century, and in February 2001, the journal Nature published its report of the first complete analysis of the human genome.

PRINCIPAL TERMS

• anticodon: a sequence of three nucleotide bases in transfer RNA (tRNA) that bonds to a complementary codon in messenger RNA (mRNA).
• codon: a sequence of three nucleotide bases that specifies a particular amino acid or control point in the process of protein synthesis.
• gene expression: the process by which RNA copies genes, which are specific segments of the DNA molecule, and uses the information to synthesize either proteins or other types of RNA.
• peptide bond: a covalent bond that links the carboxyl group of one amino acid to the amine group of another, enabling the formation of proteins and other polypeptides.
• ribosome complex: a structure consisting of ribosomal RNA (rRNA) and enzymes that decodes messenger RNA (mRNA) and coordinates the assembly of proteins from amino acids carried by transfer RNA (tRNA).

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