Gene Manifestation and Control

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Transcription

Transcription is the procedure by which DNA is replicated (transcribed) to mRNA, which carries the info needed for healthy proteins synthesis. Transcribing takes place in two extensive steps. 1st, pre-messenger RNA is formed, with the involvement of RNA polymerase enzymes. The task relies on Watson-Crick base partnering, and the resulting single strand of RNA is the reverse-complement of the first DNA pattern. The pre-messenger RNA can then be edited to produce the desired mRNA molecule within a process known asRNA splicing.

Figure 4-20

The three roles of RNA in protein synthesis. Messenger RNA (mRNA) is translated into protein by the joint action of transfer RNA (tRNA) and the ribosome, which is composed of numerous proteins and two major ribosomal RNA (rRNA) molecules. [Adapted from (more. )

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.

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.

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. How each RNA carries out its specific task is discussed in this section, while the biochemical events in protein synthesis and the required protein factors are described in the final section of the chapter.

The Protein Synthesis Machinery

In addition to the mRNA template, many molecules and macromolecules contribute to the process of translation. The composition of each component may vary across species; for instance, ribosomes may consist of different numbers of rRNAs and polypeptides depending on the organism. However, the general structures and functions of the protein synthesis machinery are comparable from bacteria to human cells. Translation requires the input of an mRNA template, ribosomes, tRNAs, and various enzymatic factors.

The Genetic code

The genetic code is almost universal. It is the basis of the transmission of hereditary information by nucleic acids in all organisms. There are four bases in RNA (A,G,C and U), so there are 64 possible triplet codes (4 3 = 64). In theory only 22 codes are required: one for each of the 20 naturally occurring amino acids, with the addition of a start codon and a stop codon (to indicate the beginning and end of a protein sequence). Many amino acids have several codes ( degeneracy ), so that all 64 possible triplet codes are used. For example Arg and Ser each have 6 codons whereas Trp and Met have only one. No two amino acids have the same code but amino acids whose side-chains have similar physical or chemical properties tend to have similar codon sequences, e.g. the side-chains of Phe, Leu, Ile, Val are all hydrophobic, and Asp and Glu are both carboxylic acids (see Figure 11). This means that if the incorrect tRNA is selected during translation (owing to mispairing of a single base at the codon-anticodon interface) the misincorporated amino acid will probably have similar properties to the intended tRNA molecule. Although the resultant protein will have one incorrect amino acid it stands a high probability of being functional. Organisms show codon bias and use certain codons for a particular amino acid more than others. For example, the codon usage in humans is different from that in bacteria; it can sometimes be difficult to express a human protein in bacteria because the relevant tRNA might be present at too low a concentration.

Figure 11 | The Genetic code triplet codon assignments for the 20 amino acids. As well as coding for methionine, AUG is used as a start codon, initiating protein biosynthesis

Transfer RNA

Transfer RNA adopts a well defined tertiary structure which is normally represented in two dimensions as a cloverleaf shape, as in Figure 7. The structure of tRNA is shown in more detail in Figure 8.

Figure 8 | Two-dimensional structures of tRNA (transfer RNA) In some tRNAs the DHU arm has only three base pairs.

Each amino acid has its own special tRNA (or set of tRNAs). For example, the tRNA for phenylalanine (tRNAPhe) is different from that for histidine (tRNAHis). Each amino acid is attached to its tRNA through the 3group to form an ester which reacts with the group of the terminal amino-acid of the growing protein chain to form a new amide bond (peptide bond) during protein synthesis (Figure 9). The reaction of esters with amines is generally favourable but the rate of reaction is increased greatly in the ribosome.

Figure 9 | Protein synthesis Reaction of the growing polypeptide chain with the 3of the charged tRNA. The amino acid is transferred from the tRNA molecule to the protein.

Each transfer RNA molecule has a well defined tertiary structure that is recognized by the enzyme aminoacyl tRNA synthetase, which adds the correct amino acid to the 3of the uncharged tRNA. The presence of modified nucleosides is important in stabilizing the tRNA structure. Some of these modifications are shown in Figure 10.

Figure 10 | Modified bases in tRNA Structures of some of the modified bases found in tRNA.

Common Misconceptions About Mutations

Something important to note is that sometimes the DNA sequence experiences an insertion or deletion of three nucleotides in a row. This doesn’t cause a frameshift mutation. Instead, it will just impact whether or not the deleted or inserted amino acids are added or not.

This can cause a dramatic change in the outcome of the polypeptide.

Another common misconception is that a mutation is always dramatic. While this is sometimes the case, mutations are common and provide the genetic variation we so appreciate in life. Many mutations have little to no impact on life, and some mutations even create good changes.

It’s a very limited number of mutations that survive to be problematic.

Translation, Elongation, and Termination

In prokaryotes and eukaryotes, the basics of elongation are the same, so we will review elongation from the perspective of E. coli . The 50S ribosomal subunit of E. coli consists of three compartments: the A (aminoacyl) site binds incoming charged aminoacyl tRNAs. The P (pept >At the. coli, fMethas the ability to of entering the S site straight without first entering the A site. Similarly, the eukaryotic Met-tRNAi, with help from other proteins of the initiation complex, binds directly to the P site. In both cases, this creates an initiation complex with a free A site ready to accept the tRNA corresponding to the first codon after the AUG.

During translation elongation, the mRNA template provides specificity. As the ribosome moves along the mRNA, each mRNA codon comes into register, and specific binding with the corresponding charged tRNA anticodon is ensured. If mRNA were not present in the elongation complex, the ribosome would bind tRNAs nonspecifically.

Elongation proceeds with charged tRNAs entering the A site and then shifting to the P site followed by the E site with each single-codon step of the ribosome. Ribosomal steps are induced by conformational changes that advance the ribosome by three bases in the 3direction. The energy for each step of the ribosome is donated by an elongation factor that hydrolyzes GTP. Pept >E. colitranslation apparatus usually takes only zero. 05 seconds to add each amino acid, and therefore a 200-amino acid proteins can be translated in just 10 seconds.



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