Each time I hear the word 'translation' I think about starting with some text written in one language and converting that text into another language. I also think about interviews on television that require an interpreter to translate the spoken language into one that I can understand. Also, from somewhere deep in my schooldays, comes the uncomfortable memory of spending long hours translating nightly assignments from Latin class into something that never sounded quite like English. Translation has always seemed an elaborate, somewhat mysterious process.
Fortunately, genetic translation, the translation of the sequence of base pairs of the DNA molecule into proteins made of amino acids, is very straightforward. There is a one-to-one correspondence of three bases for each amino acid and the sequence of these triplets (three bases) exactly matches the sequence of the final proteins. There are a few extra bells and whistles required to make the whole process work. But for the most part these are structural and provide the intermediate steps and regulation of the process.
We don't translate the entire genome into proteins. This would require the synthesis of far more protein than the earth is capable of supplying. For humans, as is true for most animals, we translate small sections of our genome into proteins. These small sections are first expressed in the form of messenger-RNA (mRNA). mRNA is made by duplicating only one string of bases from a segment of DNA. Each segment of mRNA represents the specification for a complete protein. Each mRNA strand is essentially a 'recipe' for making a protein.
The process of translating the mRNA (a sequence of nucleotides) into a protein (a sequence of amino acids) requires several intermediate constructions and a few chemical tools. The most prominent of these tools is called a ribosome. A complete ribosome (made up from two smaller subunits, a 40s subunit and a 60s subunit) seems to be the primary tool for conducting the translation of mRNA to protein. The shape of the ribosome allows a strand of mRNA to be threaded through the middle of the ribosome. As the mRNA is pushed or pulled through the center of the ribosome, a protein is constructed. Proteins (polypeptides) are built one amino acid at a time while the mRNA is advanced through the ribosome.
Whether the final protein is only a few amino acids long or a huge globular protein consisting of thousands of peptide residues, the process of adding amino acids is the same. Each amino acid is carried to the site within the ribosome by a specific transfer-RNA (tRNA). Once the process is started it proceeds until the end of the mRNA is encountered. The initiation of the process is elaborate. It requires the 40s and 60s subunits of the ribosome, the mRNA, some specific proteins, and a special methionine-bearing tRNA. This special methionine-bearing tRNA differs from the usual tRNA used to carry the individual amino acids to the synthesis site within the hollow ribosome.
Step One: A molecule of the methionine-tRNA combines with a large initiation factor molecule (eIF-2) and a molecule of guanosine triphosphate (GTP). This complex fits into the smaller fraction subunit (40s) of the ribosome. This entire complex (40s + methionine-tRNA + eIF-2 + GTP) is called the 43s preinitiation complex.
Step Two: A molecule of mRNA is bound to the 43s preinitiation complex. No one is quite sure how the proper end of the mRNA is selected. If the mRNA were somehow bound 'backwards' the subsequent protein synthesis would go astray, if it went at all. Some investigators have speculated that a special 'cap' on the starting end of some mRNA is needed to help locate and orient the mRNA for this critical initiation. But it seems that with or without these caps, the mRNA finds its way into proper position on the 43s preinitiation complex (between the 40s subunit and the eIF-2, methionine-tRNA, plus GTP complex). The mRNA seems to slide along the ribosomal subunit until the first A-U-G sequence is found. This A-U-G codon sequence is juxtaposed with the C-A-T anticodon sequence on the methionine-tRNA. Several other initiation factors may be required for this step. The energy for these machinations is provided by ATP molecules.
Step Three: The complete ribosome is now assembled. The GTP provides the energy for this step. Several smaller initiation factors are released along with the eIF-2. The two subunits, 40s and 60s of the ribosome are joined.
Step Four: The process of initiation now yields to the process of protein elongation. The combining of the two ribosome subunits encloses the mRNA. The spacing between these components is such that an additional six nucleotides (or two triplet codons) are engaged by the ribosome. This means that there are now three adjacent codon triplets on the mRNA that may attract tRNA molecules with the appropriate anticodons. Outside of the ribosome many molecules of various tRNAs are bound to their respective amino acids. These tRNAs also become bound to a complex know as an elongation factor (EF-1). The next tRNA permitted to be bound within the ribosome must have an anticodon that is compatible with the next available codon on the mRNA. The appropriate tRNA (and EF-1), with its specific amino acid 'tail' is nestled into position next to the methionine-tRNA.
Step Five: Once the tRNA is in position a GTP provides the energy to remove the EF-1 and the tRNA is bound to the codon site. The two tRNAs (the methionine-tRNA and the first amino acid tRNA) are anchored side by side at their respective codons. This positioning places the initial methionine and the first amino acid residue destined for the final protein next to each other. The two amino acids are now joined to each other. The methionine is detached from its methionine-tRNA and bound to its neighboring amino acid. The neighboring amino acid (now with the methionine attached) remains bound to its tRNA.
Step Six: The initiating tRNA that carried the methionine is now released by the ribosome. The entire ribosome with the aid of some additional elongation factors (EF-2, EF-3, etc.) moves along the mRNA until three new nucleotides are entrained. These three represent the next codon that specifies the next amino acid to be added to the growing chain of amino acids forming the final protein.
Step Seven: A repetition of steps four through seven continue to elongate the amino acid chain. Each cycle adds one new amino acid to the growing protein polypeptide chain. Thus far we have described an mRNA molecule entering a ribosome, various tRNAs carrying amino acids, one at a time, also entering the ribosome and the mRNA and a growing tail of protein exiting from the other end of the ribosome.
Step Eight: The termination of this process is signaled by the presence of an U-A-A 'termination codon'. Sometime before this step, although no definite signal has been revealed, the initial methionine is removed from the front of the amino acid chain. The presence of the termination codon allows a termination factor protein to cleave the entire amino acid polypeptide from its tRNA. Thus, the synthesized protein is released into the cytoplasm of the cell. The release of the protein into the cell is accompanied by the dissociation of the ribosome and all the above mentioned components, including the original mRNA. Although the details of some of these steps are not completely elucidated, protein synthesis, the translation of a nucleotide sequence into an amino acid sequence, occurs in a manner very similar to this description.