A-to-I RNA editing in human disease

Published on January 17, 2013   34 min

Other Talks in the Therapeutic Area: Cardiovascular & Metabolic

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Hello, I'm Kazuko Nishikura, a professor at the Wistar Institute in Philadelphia.
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Today, I'm going to talk about RNA editing. RNA editing is a post-transcriptional process that changes the nucleotide sequence of an RNA transcript, resulting in different RNA not encoded in the genomic DNA. There are many different types of RNA editing that modify transcripts of plant, animal and parasite genomes as described in Dr Stephen Hajduk's talk. One particular type of RNA editing changes adenosine to inosine. I will talk about this A-to-I RNA editing, and especially about its relevance to human diseases. ADAR (adenosine deaminase acting on RNA) is an enzyme involved
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in this A-to-I RNA editing process and converts adenosine to inosine, specifically in double-stranded RNAs through a hydrolytic deamination reaction. Inosine base-pairs with cytidine and is treated as if it were guanosine by the translation machinery. Reverse transcriptase also reads inosine as guanosine, so A-to-I RNA editing can be detected as an A-to-G change in the cDNA sequence.
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We identified the first member of the ADAR gene family ADAR1, which subsequently led to identification of two additional family members, ADAR2 and ADARs3. These ADARs are highly conserved from fish to human. ADARs share a common substrate-binding domain containing two to three repeats of a double-strand RNA binding motif and a common deaminase or catalytic domain. Additional domains are unique to each member, such as the Z DNA binding domain of ADAR1 and the arginine-lysine-rich single-strand RNA binding R-domain of ADAR3. Both ADAR1 and ADAR2 are detected in many tissues, whereas ADAR3 is expressed only in the brain.