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Collaborators:
Dr. Kenton Swartz.
Dr. Miguel Holmgren
Nitional Institute of Health (NIH) |
Dr. Josh
Rosenthal
Regulation of excitability by RNA editing
All
modern biology is based on the principle that genetic information
is stored in genes and realized in proteins. Surprisingly, recent
genome sequencing projects indicate that drastically different
organisms, such as humans, flies and worms, carry a more or
less common set of genes. What then is the genetic basis of
complexity? RNA editing, a process that changes and increases
genetic information, could obviously play an important role,
however its biological significance remains poorly understood.
One form of editing, mediated by the hydrolytic deamination
of adenosine (A) residues in mRNAs, is prevalent in the nervous
system of all metazoans. By changing A to Inosine
(I), which is read by the ribosome as guanine (G), codons
can be mutated and protein structure and function changed. In
mammals, relatively few mRNA substrates for A®I editing have
been identified, most encoding proteins involved in synaptic
transmission. More recent investigations, however, have identified
a surprisingly large number of substrates in Drosophila
and Loligo, suggesting that
editing in invertebrates is a particularly robust process. Editing
permits multiple proteins from a single gene. Which mRNAs are
targeted and how is protein function changed? My research examines
RNA editing in the squid giant axon and specifically focuses
on voltage dependent K+ channels, the Na+/K+
ATPase and double-stranded RNA specific adenosine deaminase, and editing enzyme. Molecular biological and
biochemical techniques are used to examine how the editing of
transcripts for these proteins is regulated. Biophysical techniques
are used to understand how changes made by editing affect channel
and transporter function. These data are important because they
provide a window on how A®I editing influences the evolution
of nervous function.
Funding-
Active
Regulation of the Na/K pump by RNA editing
PI: Joshua Rosenthal, Program Director: Walter Frontera
Period: 12/01/04 - 11/30/09
Granting agency: NIH-NINDS SNRP Program.
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