Synthesizing a protein molecule requires that the correct amino acid building blocks be present in the cytoplasm. Furthermore, these amino acids must align int he proper sequence along a strand of messenger RNA. A second kind of RNA molecule, synthesized in the nucleus and called transfer RNA (tRNA), aligns amino acids in a way that enables them to bond to each other. A transfer RNA molecule consists of only seventy to eighty nucleotides and has a complex three-dimensional shape. The two ends of the tRNA molecule are most important for the "connector" function.
At one end, each transfer RNA molecule has a specific binding site for a particular amino acid. There is at least one type of transfer RNA molecule for each of the twenty amino acids. Before the transfer RNA can pick up its amino acid, the amino acid must be activated. Special enzymes catalyze this step. ATP provides the energy to form a bond between the amino acid and its transfer RNA molecule.
The other end of each transfer RNA molecule includes a region, called the anticodon, that contains three nucleotides in a particular sequence unique to that type of transfer RNA. These nucleotides bond only to a specific complementary mRNA codon. In this way, the appropriate transfer RNA carries its amino acid to the correct place in the sequence, as prescribed by the mRNA.
Although there are only 20 amino acids to be coded for, four bases can combine in triplets 64 different ways, so there are 64 different codons possible and all of them occur in mRNA. Because 3 of these codons do not have a corresponding transfer RNA, when they occur they provide a "stop" signal, indicating the end of protein synthesis, much like the period at the end of this sentence. A total of 61 different transfer RNAs are specific for the remaining 61 codons, which means that more than one type of tRNA can correspond to the same amino acid type. Because a given amino acid can be specified by more than one codon, the genetic code is said to be "degenerate." However, each type of tRNA can bind only its one particular amino acid, so the instructions are precise, and the corresponding codon will code only for that amino acid.
The binding of tRNA and mRNA occurs in close association with a ribosome. A ribosome is a tiny particle of two unequal-sized subunits composed of ribosomal RNA (rRNA) and protein. The smaller subunit of a ribosome binds to a molecule of messenger RNA near the codon at the beginning of the messenger strand. This action allows a transfer RNA molecule with the complementary anticodon to bring the amino acid it carries into position and temporarily join to the ribosome. A second transfer RNA molecule, complementary to the second codon on mRNA, then binds (with its activated amino acid) to an adjacent site on the ribosome. The first transfer RNA molecule then releases its amino acid, providing the energy for a peptide bond to form between the two amino acids. This process repeats again and again as the ribosome moves along the messenger RNA, adding amino acids one at a time to the developing polypeptide molecule. The enzymatic activity necessary for bonding of the amino acids comes from ribosomal proteins and some RNA molecules (ribozymes) in the larger subunit of the ribosome. This subunit also holds the growing chain of amino acids.
A molecule of messenger RNA usually associates with several ribosomes at the same time. Thus, several copies of that protein, each in a different stage of formation, may be present at any given moment.
As the polypeptide forms, proteins called chaper-ones fold it into its unique shape, and when the process is completed, the polypeptide is released as a separate functional molecule. The transfer RNA molecules, ribosomes, mRNA, and the enzymes can function repeatedly in protein synthesis.
ATP molecules provide the energy for protein synthesis. Because a protein may consist of many hundreds of amino acids and the energy from three ATP molecules is required to link each amino acid to the growing chain, a large fraction of a cell's energy supply supports protein synthesis.
The quantity of a particular protein that a cell synthesizes is generally proportional to the quantity of the corresponding messenger RNA molecules present. The rate at which messenger RNA is transcribed from DNA in the nucleus and the rate at which enzymes (ribonucleases) destroy the messenger RNA in the cytoplasm therefore controls protein synthesis.
Proteins called transcription factors activate certain genes, thereby controlling which proteins a cell produces and how many copies form. A connective tissue cell might have many messenger RNAs representing genes that encode the protein collagen; a muscle cell would have abundant messenger RNAs encoding muscle proteins. Extracellular signals such as hormones and growth factors activate transcription factors.