From RNA to Protein Synthesis

DNA stores the information for protein synthesis and RNA carries out the instructions encoded in DNA, most biological activities are carried out by proteins. The accurate synthesis of proteins thus is critical to the proper functioning of cells and organisms.

the linear order of amino acids in each protein determines its three-dimensional structure and activity. For this reason, assembly of amino acids in their correct order, as encoded in DNA, is the key to production of functional proteins.



Three kinds of RNA molecules perform different but cooperative functions in protein synthesis

1. Messenger RNA (mRNA) carries the genetic information copied from DNA in the form of a series of three-base code “words,” each of which specifies a particular amino acid.

2. Transfer RNA (tRNA) is the key to deciphering the code words in mRNA. Each type of amino acid has its own type of tRNA, which binds it and carries it to the growing end of a polypeptide chain if the next code word on mRNA calls for it. The correct tRNA with its attached amino acid is selected at each step because each specific tRNA molecule contains a three-base sequence that can base-pair with its complementary code word in the mRNA.

3. Ribosomal RNA (rRNA) associates with a set of proteins to form ribosomes. These complex structures, which physically move along an mRNA molecule, catalyze the assembly of amino acids into protein chains. They also bind tRNAs and various accessory molecules necessary for protein synthesis. Ribosomes are composed of a large and small subunit, each of which contains its own rRNA molecule or molecules.



Translation is the whole process by which the base sequence of an mRNA is used to order and to join the amino acids in a protein. The three types of RNA participate in this essential protein-synthesizing pathway in all cells; in fact, the development of the three distinct functions of RNA was probably the molecular key to the origin of life.


RNA contains ribonucleotides of adenine, cytidine, guanine, and uracil; DNA contains deoxyribonucleotides of adenine, cytidine, guanine, and thymine. Because 4 nucleotides, taken individually, could represent only 4 of the 20 possible amino acids in coding the linear arrangement in proteins, a group of nucleotides is required to represent each amino acid. The code employed must be capable of specifying at least 20 words (i.e., amino acids).

If two nucleotides were used to code for one amino acid, then only 16 (or 42) different code words could be formed, which would be an insufficient number. However, if a group of three nucleotides is used for each code word, then 64 (or 43) code words can be formed. Any code using groups of three or more nucleotides will have more than enough units to encode 20 amino acids. Many such coding systems are mathematically possible. However, the actual genetic code used by cells is a triplet code, with every three nucleotides being “read” from a specified starting point in the mRNA. Each triplet is called a codon. Of the 64 possible codons in the genetic code, 61 specify individual amino acids and three are stop codons. most amino acids are encoded by more than one codon. Only two — methionine and tryptophan — have a single codon; at the other extreme, leucine, serine, and arginine are each specified by six different codons. The different codons for a given amino acid are said to be synonymous. The code itself is termed degenerate, which means that it contains redundancies.

Synthesis of all protein chains in prokaryotic and eukaryotic cells begins with the amino acid methionine. In most mRNAs, the start (initiator) codon specifying this aminoterminal methionine is AUG. In a few bacterial mRNAs, GUG is used as the initiator codon, and CUG occasionally is used as an initiator codon for methionine in eukaryotes. The three codons UAA, UGA, and UAG do not specify amino acids but constitute stop (terminator) signals that mark the carboxyl terminus of protein chains in almost all cells. The sequence of codons that runs from a specific start site to a terminating codon is called a reading frame. This precise linear array of ribonucleotides in groups of three in mRNA specifies the precise linear sequence of amino acids in a protein and also signals where synthesis of the protein chain starts and stops.

Because the genetic code is a commaless, overlapping triplet code, a particular mRNA theoretically could be translated in three different reading frames. Indeed some mRNAs have been shown to contain overlapping information that can be translated in different reading frames, yielding different polypeptides.The vast majority of mRNAs, however, can be read in only one frame because stop codons encountered in the other two possible reading frames terminate translation before a functional protein is produced. Another unusual coding arrangement occurs be- cause of frameshifting. In this case the protein-synthesizing machinery may read four nucleotides as one amino acid and then continue reading triplets, or it may back up one base and read all succeeding triplets in the new frame until termination of the chain occurs. These frameshifts are not common events, but a few dozen such instances are known

The vast majority of mRNAs, however, can be read in only one frame because stop codons encountered in the other two possible reading frames terminate translation before a functional protein is produced. Another unusual coding arrangement occurs be- cause of frameshifting. In this case the protein-synthesizing machinery may read four nucleotides as one amino acid and then continue reading triplets, or it may back up one base and read all succeeding triplets in the new frame until termination of the chain occurs. These frameshifts are not common events, but a few dozen such instances are known

The Folded Structure of tRNA Promotes Its Decoding Functions

understanding the flow of genetic information from DNA to protein was to determine how the nucleotide sequence of mRNA is converted into the amino acid sequence of protein. This decoding process requires two types of adapter molecules: tRNAs and enzymes called aminoacyl-tRNA synthetases.

All tRNAs have two functions: to be chemically linked to a particular amino acid and to base-pair with a codon in mRNA so that the amino acid can be added to a growing peptide chain. Each tRNA molecule is recognized by one and only one of the 20 aminoacyl-tRNA synthetases. Likewise, each of these enzymes links one and only one of the 20 amino acids to a particular tRNA, forming an aminoacyl-tRNA. Once its correct amino acid is attached, a tRNA then recognizes a codon in mRNA, thereby delivering its amino acid to the growing polypeptide.

Ribosomes Are Protein-Synthesizing Machines

If the many components that participate in translating mRNA had to interact in free solution, the likelihood of simultaneous collisions occurring would be so low that the rate of amino acid polymerization would be very slow. The efficiency of translation is greatly increased by the binding of the mRNA and the individual aminoacyl-tRNAs to the most abundant RNA-protein complex in the cell — the ribosome. This two-part machine directs the elongation of a polypeptide at a rate of three to five amino acids added per second. Small proteins of 100 – 200 amino acids are therefore made in a minute or less. On the other hand, it takes 2 to 3 hours to make the largest known protein, titin, which is found in muscle and contains 30,000 amino acid residues. The machine that accomplishes this task must be precise and persistent.

A ribosome is composed of several different ribosomal RNA (rRNA) molecules and more than 50 proteins, organized into a large subunit and a small subunit. The proteins in the two subunits differ, as do the molecules of rRNA. The small ribosomal subunit contains a single rRNA molecule, referred to as small rRNA; the large subunit contains a molecule of large rRNA and one molecule each of two much smaller rRNAs in eukaryotes.The lengths of the rRNA molecules, the quantity of proteins in each subunit, and consequently the sizes of the subunits differ in prokaryotic and eukaryotic cells. (The small and large rRNAs are about 1500 and 3000 nucleotides long in bacteria and about 1800 and 5000 nucleotides long in humans.) Perhaps of more interest than these differences are the great structural and functional similarities among ribosomes from all species. This consistency is another reflection of the common evolutionary origin of the most basic constituents of living cells.

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