RNA Editing
Because rRNAs and tRNAs are non-coding chemical modification to their nucleotides affect only the structural feature and possibly catalytic activities of the molecules, With mRNAs the situation is very different: chemical modification has the potential of change the coding properties of the transcript, resulting in an equivalent alteration in the amino acid sequence of the protein that is specified.
A notable example of RNA editing occurs with the human mRNA for apolipoprotein B. The gene for this protein codes for a 456-amino-acid polypeptide, called apolipoprotein B100, which is synthesize: d in liver cells and secreted into the bloodstream where it transports lipids around the body. A related protein, apolipoprotein B48, is made by intestinal cells.
This protein is only 2153 amino acids in length and is synthesized from an edited version of the mRNA for the full-length protein. In intestinal cells this mRNA is modified by deamination of a cytosine, converting this into n uracil.
This changes a CAA codon, specifying glutamine, into a UAA codon, which causes translation to stop, resulting in the truncated protein. The deamination is carried out by an l{NA-binding enzyme which, in conjunction with a set of auxiliary protein factors, binds to a sequence immediately downstream of the modification position within the mRNA (Smith and Sowden, 1996). Although not common,
RNA editing occurs in a number of different organisms and includes a variety of different nucleotide changes. Some editing events have a significant impact on the organism: in humans, editing is partly responsible for the generation of antibody diversity (Neuberger and Scott, 2000; Section 12.2.1) and has also been implicated in control of the HIV-1 infection cycle (Bourara et aI" 2000). One particularly interesting type of editing is the deamination of adenosine to inosine, which is carried out by enzymes called adenosine deaminases acting on RNA (AGARs) (Reenan, 2001).
Some of the target mRNAs for these enzymes are selectively edited at a limited number of positions, These positions are apparently specified by double-stranded segments of the pre-mRNA, formed by base-pairing between the modification site and sequences from adjacent introns. This type of editing occurs for example, during processing of the mRNAs for mammalian glutamate receptors (Scott, 1997). Selective editing contrasts with the second type of modification carried out by ADARs, in which the target molecules become extensively deaminated, over 50% of the adenosines in the RNA becoming converted to inosines. Hyperediting has so far been observed mainly, but not exclusively, with viral RNAs and is thought to occur by chance, these RNAs adopting base-paired structures that fortuitously act ns substrates for ADAR. It may, however physiological importance in the etiology of disease caused by the edited viruses.
This possibility is raised by the discovery that viral RNAs associated with persistent measles infections (as opposed to the more usual transient version of the disease) are hyperedited (Bass, 1997)
Because rRNAs and tRNAs are non-coding chemical modification to their nucleotides affect only the structural feature and possibly catalytic activities of the molecules, With mRNAs the situation is very different: chemical modification has the potential of change the coding properties of the transcript, resulting in an equivalent alteration in the amino acid sequence of the protein that is specified.
A notable example of RNA editing occurs with the human mRNA for apolipoprotein B. The gene for this protein codes for a 456-amino-acid polypeptide, called apolipoprotein B100, which is synthesize: d in liver cells and secreted into the bloodstream where it transports lipids around the body. A related protein, apolipoprotein B48, is made by intestinal cells.
This protein is only 2153 amino acids in length and is synthesized from an edited version of the mRNA for the full-length protein. In intestinal cells this mRNA is modified by deamination of a cytosine, converting this into n uracil.
This changes a CAA codon, specifying glutamine, into a UAA codon, which causes translation to stop, resulting in the truncated protein. The deamination is carried out by an l{NA-binding enzyme which, in conjunction with a set of auxiliary protein factors, binds to a sequence immediately downstream of the modification position within the mRNA (Smith and Sowden, 1996). Although not common,
RNA editing occurs in a number of different organisms and includes a variety of different nucleotide changes. Some editing events have a significant impact on the organism: in humans, editing is partly responsible for the generation of antibody diversity (Neuberger and Scott, 2000; Section 12.2.1) and has also been implicated in control of the HIV-1 infection cycle (Bourara et aI" 2000). One particularly interesting type of editing is the deamination of adenosine to inosine, which is carried out by enzymes called adenosine deaminases acting on RNA (AGARs) (Reenan, 2001).
Some of the target mRNAs for these enzymes are selectively edited at a limited number of positions, These positions are apparently specified by double-stranded segments of the pre-mRNA, formed by base-pairing between the modification site and sequences from adjacent introns. This type of editing occurs for example, during processing of the mRNAs for mammalian glutamate receptors (Scott, 1997). Selective editing contrasts with the second type of modification carried out by ADARs, in which the target molecules become extensively deaminated, over 50% of the adenosines in the RNA becoming converted to inosines. Hyperediting has so far been observed mainly, but not exclusively, with viral RNAs and is thought to occur by chance, these RNAs adopting base-paired structures that fortuitously act ns substrates for ADAR. It may, however physiological importance in the etiology of disease caused by the edited viruses.
This possibility is raised by the discovery that viral RNAs associated with persistent measles infections (as opposed to the more usual transient version of the disease) are hyperedited (Bass, 1997)
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