Adenosine deaminase enzymes that act upon RNA (ADAR) have
been shown to play a critical role in mammalian development. ADAR is responsible for the conversion of
adenosine to inosine in double-stranded RNA (dsRNA).
 |
Adenosine |
 |
Inosine |
Literally hundreds of thousands of these transforming events
have been reported within human cells.
This editing appears to occur predominantly in noncoding repetitive
elements within the genome. Additionally,
there are three forms of ADAR that have been identified – ADAR1, ADAR2 and
ADAR3. They seem to be widely expressed
during early development especially in the embryonic and post-natal development
period. To date, of the three forms of
ADAR, only ADAR1 and ADAR2 have been shown to demonstrate enzymatic activity on
natural substrates in vitro.
Using the mouse animal model, ADAR2 has been shown to modify
an essential receptor in the brain. Experimental
animals who die from seizures have successfully rescued when a genomic
substitution mimicked the adenosine to inosine modification of the RNA
transcript. This result proved to be an
elegant demonstration of the mode of action of ADAR2 in vivo.
The role of ADAR1 within the living organism remained
unknown. This prompted Dr. Brian J.
Liddicoat and his colleagues from the Department of Medicine at St. Vincent’s
Hospital University of Melbourne, Australia to engage in an elaborate experimental
investigation to uncover its role.
The results of their extensive efforts demonstrated that, “The
A-to-I editing of ADAR1 is essential for embryonic development and the
maintenance of hematopoiesis in vivo.”
Hematopoiesis refers to the production of viable circulating blood
cells.
This is an important finding and is a significant
contribution to the overall understanding of the complexities and intricacies
of mammalian development.
