The discovery of RNA editing in the mid-1980s involved mitochondrial mRNAs of trypanosomes. This protozoan causes sleeping sickness. The nucleotides get inserted or deleted post-transcriptionally through RNA editing. Alternatively, it leads to the conversion of one base to another. After completion of the transcription, the uridines get inserted into mRNA. It inserts cytidines and deletes a few bases. RNA editing also uses a group of RNAs known as guide RNAs. An RNA molecule consists of uracil, adenine, guanine, and cytosine. The uracil gets incorporated into an RNA molecule through the RNA editing process.
Image: RNA editing
RNA editing in humans:
RNA editing occurs in human mRNA for apolipoprotein B. The gene encoding the protein also codes for an amino acid polypeptide known as apolipoprotein B48. The intestinal cells synthesize this protein. Deamination of a cytosine causes conversion of cytosine to uracil. Thus, a CAA codon gets converted into a UAA codon. RNA editing plays an important role in creating diverse antibodies. It also plays an important role in controlling the HIV infection cycle. Adenosine deaminase acts on RNA and carries out deamination of adenosine to inosine. The adenosine deaminases are known as Adenosine Deaminases Acting on RNAs (ADARs).
Other examples of RNA editing in mammals include tissues such as intestinal, muscular tissues, testis, tumors, B lymphocytes, and brain cells. The changes occurring due to the conversion of the cytosine to uracil involve apolipoprotein B mRNA. There exist other target RNAs too. The mRNA in muscle is known as alpha-galactosidase mRNA. It changes uridine to adenine. It converts a phenylalanine codon to a tyrosine codon. Wilm’s tumor mRNA is an example of target RNA for testicular tumor involving the conversion of uridine to cytidine. Hence, a leucine codon gets converted to a proline codon. B-lymphocytes consist of immunoglobulin mRNAs transcribed into immunoglobulins or antibodies. Changes in the mRNA lead to antibody diversity. ADAR editing occurs before intron splicing. Some nucleotides within the introns also undergo the process of editing. RNA editing inspires molecular diversity and hence classified under the epigenetic modification in some cases.
A nonclassic conversion of G to A occurs in hnRNPK in malignant colorectal samples. Originally the RNA editing system must be an evolutionary event in animals.
What is gRNA?
Guide RNAs or gRNAs guide in the insertion or deletion of uridine nucleotide residues into mitochondrial mRNAs. They boost the process of RNA editing. Guide RNAs not only guide RNA editing but also guide DNA editing. Guide RNA editing is uncommon in humans and mostly seen in trypanosomes.
Human transcriptomes reveal abundant A to I editing sites:
Previous bioinformatics methods were not so efficient in determining A to I sites. These methods possessed a risk of mistakenly identifying false single nucleotide polymorphisms (SNPs) as RNA editing sites. However, sophisticated algorithms with regulated accuracies for sequence alignment and comparison addressed this problem. The comparison studies included two main elements. The genomes alignment consisted of human expressed sequence tags (ESTs) and cDNA. Do you know what an expressed sequence tag is? An EST is a unique DNA sequence derived from a cDNA library or a sequence transcribed into a tissue. The element order depended on the sequence similarity. The designing of the algorithm helped in removing single nucleotide polymorphisms, random mismatches, and mutations, sequencing errors, and searched only for reverse complement alignments. The algorithms revealed many A to I editing sites in thousands of genes.
RNA editing in Alu elements:
An ALU family involves a dispersed intermediately repetitive DNA sequence found in the human genome. About three thousand copies of these elements constitute a genome. Many human A to I RNA editing sites exist.
Is RNA editing a cure for diseases?
Unlike DNA editing, RNA editing helps in tweaking the gene expression instead of interfering with the genome and making permanent changes to it.
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