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RNA Editing - Mechanisms, Features and Significance

BY: Dr. Suresh Kaushik | Category: DNA | Submitted: 2013-03-07 12:03:08
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Article Summary: "The information flows directly from DNA to protein through the RNA intermediate molecule. But, it has been discovered that the information that is contained in the DNA is not always found in the RNA products used to make proteins. Mitochondria and chloroplast contain the biochemical machinery to alter the sequence of the final t.."


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The central dogma of molecular genetics states that the information that is found in DNA is used to produce mRNA molecules that are instrumental in the production of proteins. Therefore, the information flows directly from DNA to protein through the RNA intermediate molecule. But, it has been discovered that the information that is contained in the DNA is not always found in the RNA products used to make proteins. Mitochondria and chloroplast contain the biochemical machinery to alter the sequence of the final transcription product. This process is called RNA editing. Such changes have been observed in tRNA, rRNA and mRNA molecules of eukaryotes, but not prokaryotes. RNA editing occurs in the cell nucleus, cytosol, as well as in mitochondria and plastids.The diversity of RNA editing mechanisms includes nucleoside modifications such as C to U and A to I deaminations, as well as non-template nucleotide additions and insertions. RNA editing in mRNAs effectively alters the amino acid sequence of the encoded protein so that it differs from that predicted by the genomic DNA sequence.

There are mainly two mechanisms for RNA editing:

Substitution Editing: chemical alteration of individual nucleotides. These alterations are catalyzed by enzymes that recognize a specific target sequence of nucleotides e.g. cytidine deaminases that convert a C in the RNA to uracil (U) and adenosine deaminases that convert an A to inosine (I), which the ribosome translates as a G. So, a CAG codon (for Gln) can be converted to a CGG codon (for Arg).
Insertion/Deletion Editing: insertion or deletion of nucleotides in the RNA. These alterations are mediated by guide RNA (gRNA) molecules that base-pair with the RNA to be edited and serve as a template for the addition (or removal) of nucleotides in the target
Sequence analysis of a number of cytochrome c oxidase subunit II genes from non-plant species revealed that a tryptophan residue was invariant at several locations in the final protein product. But sequence analysis of this gene in several plant species revealed arginine at those positions. This amino acid change would cause a radical alteration in protein structure because an acidic amino acid would replace a neutral, hydrophobic amino acid.
Since a single base pair change in the codons for the two amino acids could generate this change (CGG for UGG), it was suggested that CGG encoded for tryptophan and not arginine in plant mitochondria. But this change in codon usage was not universal, that is some CGG codons actually specified arginine in the final protein product.

By sequencing the mRNA products for cytochrome c oxidase subunit II genes, it was found that in the mRNA the cytosine residue had been changed (edited) to uridine at the sequence location where the invariant tryptophan residue is found. This changed the codon at that location to UGG which is recognized by a tRNA that carries the amino acid tryptophan. An analysis of three other plant mitochondrial genes where the same altered codon usage was predicted suggested that mRNA editing was also occurring at the codon and that a cytosine residue was edited to uridine.

Some important features are:

• Editing can occur in both mitochondria and chloroplasts
• Plant mitochondria do not use the universal genetic code.
• The RNA editing events occur at random in the transcript.
• Both 5' and 3' non-coding regions of mRNAs may undergo editing.
• Structural RNAs such as tRNAs and rRNAs are also affected.
• Editing can convert a tryptophan codon to a arginine codon (CGG to UGG).
• Start AUG codon can be created from threonine codon (ACG)
• Stop codons can be created by editing CAG, CAA and CGA codons.
• The most frequent amino acid substations derived from RNA editing are Pro to Leu, Ser to Leu and Ser to Phe.

Significance:

The primary benefit of RNA editing could be evolutionary conservation of protein structure. For example, bound copper is required for the funciton of cytochrome c oxidase subunit II (coxII). After editing, all amino acids at the number 228 position are converted to cysteine, an amino acid required for copper (Cu) to bind. In all species except for plants, the coxII gene encodes for methionine at codon number 235. In plants, this methionine is generated by RNA editing. These events suggest that this protein is under very strong structural and functional constraints.

About Author / Additional Info:
http://www.linkedin.com/in/sureshkaushik

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