Suppressor Mutations Can Counteract Some of the Effects of Missense Nonsense Frameshift Mutations

The above discussion of the altered protein products of gene mutations is based on the presence of normally functioning tRNA molecules. However, in prokaryotic and lower eukaryotic organisms, abnormally functioning tRNA molecules have been discovered that are themselves the results of mutations. Some of these abnormal tRNA molecules are capable of binding to and decoding altered codons, thereby suppressing the effects of mutations in distant structural genes. These suppressor tRNA molecules, usually formed as the result of alterations in their anticodon regions, are capable of suppressing missense mutations, nonsense mutations, and frameshift mutations. However, since the suppressor tRNA molecules are not capable of distinguishing between a normal codon and one resulting from a gene mutation, their presence in a cell usually results in decreased viability. For instance, the nonsense suppressor tRNA molecules can suppress the normal termination signals to allow a read-through when it is not desirable. Frameshift suppressor tRNA molecules may read a normal codon plus a component of a juxtaposed codon to provide a frameshift, also when it is not desirable. Suppressor tRNA molecules may exist in mammalian cells, since read-through transcription occurs.

Normal

Wild type mRNA 5'... UAG Polypeptide uuuG AUG GCC UCU UGC AAA ggc uau agu

Met-Ala-Ser-Cys-Lys-Gly-Tyr-Ser-

Example 1 Deletion (-1)

mRNA 5'... uAG Polypeptide

Example 2 Deletion (- 3)

mRNA 5'... uAG Polypeptide uuuG

AUG Met-

GCC Ala cuu

GCA Ala

AAG Lys

Guu Val

uuug auG GCC

Met Ala

UCU Ser

AAA Lys

V Garbled

GGC uau agu agu uAG... Gly Try Ser Ser STOP

Example 3 Insertion (+1)

mRNA 5'... uAG Polypeptide

Example 4

mRNA 5'... uAG Polypeptide uuuG AuG GCC CuC uuG CAA AGG CuA uAG uAG uuAG... 3'

Met-Ala-Leu-Leu-Gln-Arg-Leu

STOP

Y Garbled uuug auG GCC ucu uuG Caa AGG uau agu agu

Met Ala Ser-Leu-Gln-Arg Tyr Ser Ser

Figure 38-5. Examples of the effects of deletions and insertions in a gene on the sequence of the mRNA transcript and of the polypeptide chain translated therefrom. The arrows indicate the sites of deletions or insertions, and the numbers in the ovals indicate the number of nucleotide residues deleted or inserted. Blue type indicates amino acids in correct order.

LIKE TRANSCRIPTION, PROTEIN SYNTHESIS CAN BE DESCRIBED IN THREE PHASES: INITIATION, ELONGATION, & TERMINATION

The general structural characteristics of ribosomes and their self-assembly process are discussed in Chapter 37. These particulate entities serve as the machinery on which the mRNA nucleotide sequence is translated into the sequence of amino acids of the specified protein.

The translation of the mRNA commences near its 5' terminal with the formation of the corresponding amino terminal of the protein molecule. The message is read from 5' to 3', concluding with the formation of the carboxyl terminal of the protein. Again, the concept of polarity is apparent. As described in Chapter 37, the transcription of a gene into the corresponding mRNA or its precursor first forms the 5' terminal of the RNA molecule. In prokaryotes, this allows for the beginning of mRNA translation before the transcription of the gene is completed. In eukaryotic organisms, the process of transcription is a nuclear one; mRNA translation occurs in the cytoplasm. This precludes simultaneous transcription and translation in eukaryotic organisms and makes possible the processing necessary to generate mature mRNA from the primary transcript—hnRNA.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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