During the 1950s and 1960s, it became apparent that DNA is essential in the synthesis of proteins. Among many functions, proteins can serve as enzymes and as structural materials in cells. Many specialized proteins function in cellular activities. For example, in humans, the hormone insulin and the muscle cell filaments are composed of protein. The hair, skin, and nails of humans are composed of proteins, as are all the hundreds of thousands of enzymes in the body.
The key to a protein molecule is how the amino acids are linked. The sequence of amino acids in a protein is a type of code that specifies the protein and distinguishes one protein from another. A genetic code in the DNA determines this amino acid code. The genetic code consists of the sequence of nitrogenous bases in the DNA. How the nitrogenous base code is translated to an amino acid sequence in a protein is the basis for protein synthesis.
For protein synthesis to occur, several essential materials must be present, such as a supply of the 20 amino acids, which comprise most proteins. Another essential component is a series of enzymes that will function in the process. DNA and another form of nucleic acid called ribonucleic acid (RNA) are essential.
RNA is the nucleic acid that carries instructions from the nuclear DNA into the cytoplasm, where protein is synthesized. RNA is similar to DNA, with two exceptions. First, the carbohydrate in RNA is ribose rather than deoxyribose, and second, RNA nucleotides contain the pyrimidine uracil rather than thymine.
Types of RNA
In the synthesis of protein, three types of RNA function. The first type is called ribosomal RNA (rRNA). This form of RNA is used to manufacture ribosomes. Ribosomes are ultramicroscopic particles of rRNA and protein. They are the places (the chemical “workbenches”) where amino acids are linked to one another to synthesize proteins. Ribosomes are found in large numbers along the membranes of the endoplasmic reticulum and in the cytoplasm of the cell (see Chapter 3).
A second important type of RNA is transfer RNA (tRNA). Transfer RNA exists in the cell cytoplasm and carries amino acids to the ribosomes for protein synthesis. When protein synthesis is taking place, enzymes link tRNA molecules to amino acids in a highly specific manner. For example, tRNA molecule X will link only to amino acid X; tRNA molecule Y will link only to amino acid Y.
The third form of RNA is messenger RNA (mRNA). In the nucleus, messenger RNA is constructed from DNA’s code of base pairs and carries the code into the cytoplasm or to the rough endoplasmic reticulum where protein synthesis takes place. Messenger RNA is synthesized in the nucleus using the DNA molecules. During the synthesis, the genetic information is transferred from the DNA molecule to the mRNA molecule. In this way, a genetic code can be used to synthesize a protein in a distant location. RNA polymerase, an enzyme, accomplishes mRNA, tRNA, and rRNA synthesis.
There are also non-coding RNA molecules (ncRNAs), which are not directly involved in protein synthesis. These will be further discussed in the section “Gene Control,” later in this chapter
Transcription
Transcription is one of the first processes in the mechanism of protein synthesis. In transcription, a complementary strand of mRNA is synthesized according to the nitrogenous base code of DNA. To begin, the enzyme RNA polymerase binds to an area of one of the DNA molecules in the double helix. (During transcription, only one DNA strand serves as a template for RNA synthesis. The other DNA strand remains dormant.) The enzyme moves along the DNA strand and “reads” the nucleotides one by one. Similar to the process of DNA replication, the new nucleic acid strand elongates in a 5'-3' direction, as shown in Figure 10-2. The enzyme selects complementary bases from available nucleotides and positions them in an mRNA molecule according to the principle of complementary base pairing. The chain of mRNA lengthens until a “stop” message is received.
Figure 10-2 The process of transcription. The DNA double helix opens, and the enzyme RNA polymerase synthesizes a molecule of mRNA according to the base sequence of the DNA template.
The nucleotides of the DNA strands are read in groups of three. Each group is a codon. Thus, a codon may be CGA, or TTA, or GCT, or any other combination of the four bases, depending on the codon’s complementary sequence in the DNA strand. Each codon will later serve as a “code word” for an amino acid. First, however, the codons are transcribed to the mRNA molecule. Thus, the mRNA molecule consists of nothing more than a series of codons received from the genetic message in the DNA.
After the “stop” codon is reached, the synthesis of the mRNA comes to an end. The mRNA molecule leaves the DNA molecule, and the DNA molecule rewinds to form a double helix. Meanwhile, the mRNA molecule passes through a pore in the nucleus and proceeds into the cellular cytoplasm, where it moves toward the ribosomes located in the cytoplasm or on the rough endoplasmic reticulum.
Translation
The genetic code is transferred to an amino acid sequence in a protein through the translation process, which begins with the arrival of the mRNA molecule at the ribosome. While the mRNA was being synthesized, tRNA molecules were uniting with their specific amino acids according to the activity of specific enzymes. The tRNA molecules then began transporting their amino acids to the ribosomes to meet the mRNA molecule.
After it arrives at the ribosomes, the mRNA molecule exposes its bases in sets of three, the codons. Each codon has a complementary codon called an anticodon on a tRNA molecule. When the codon of the mRNA molecule complements the anticodon on the tRNA molecule, the latter places the particular amino acid in that position. Then the next codon of the mRNA is exposed, and the complementary anticodon of a tRNA molecule matches with it. The amino acid carried by the second tRNA molecule is positioned next to the first amino acid, and the two are linked. At this point, the tRNA molecules release their amino acids and return to the cytoplasm to link up with new molecules of amino acid.
When it’s time for the next amino acid to be positioned in the growing protein, a new codon on the mRNA molecule is exposed, and the complementary three-base anticodon of a tRNA molecule positions itself opposite the codon. This brings another amino acid into position, and that amino acid links to the previous amino acids. The ribosome moves farther down the mRNA molecule and exposes another codon, which attracts another tRNA molecule with its anticodon.
One by one, amino acids are added to the growing chain until the ribosome has moved down to the end of the mRNA molecule. Because of the specificity of tRNA molecules for their individual amino acids, and because of the base pairing between codons and anticodons, the sequence of codons on the mRNA molecule determines the sequence of amino acids in the protein being constructed. And because the codon sequence of the mRNA complements the codon sequence of the DNA, the DNA molecule ultimately directs the amino acid sequencing in proteins. The primary “start” codon on an mRNA molecule is AUG, which codes for the amino acid methionine. Therefore, each mRNA transcript begins with the AUG codon, and the resulting polypeptide begins with methionine.
Figure 10-3 shows that the process of protein synthesis begins with the production of mRNA (upper right). The mRNA molecule proceeds to the ribosome, where it meets tRNA molecules carrying amino acids (upper left). The tRNA molecule has a base code (anticodon) that complements the mRNA code (codon) and thereby brings a specific amino acid into position. The amino acids join together in peptide bonds (bottom), and the tRNA molecules are released to pick up additional amino acid molecules.
After the protein has been synthesized completely, it is removed from the ribosome for further processing and to perform its function. For example, the protein may be stored in the Golgi apparatus before being released by the cell, or it may be stored in the lysosome as a digestive enzyme. Also, a protein may be used in the cell as a structural component, or it may be released as a hormone, such as insulin. After synthesis, the mRNA molecule breaks up and the nucleotides return to the nucleus. The tRNA molecules return to the cytoplasm to unite with other molecules of amino acids, and the ribosome awaits the arrival of a new mRNA molecule.
Figure 10-3 The process of protein synthesis.