Joshua Rosenthal, Assistant Professor Medical Sciences Campus, University of Puerto Rico. Telephone: (787) 724-1543 Mailing Address: Institute of Neurobiology 201 Blvd. Del Valle San Juan, PR 00901 E-Mail:rosenthal.joshua@gmail.com

All modern biology is based on the principle that information is stored in genes and realized in proteins. It would be logical to assume that the number of genes in an organism should scale with the organism's complexity. Surprisingly, recent genome sequencing projects do not support this hypothesis. Drastically different organisms, such as humans, flies and worms, carry a more or less common set of genes. What then is the genetic basis for complexity? RNA editing, a process that changes and increases genetic information, could play an important role. My lab focuses on a form of editing mediated by the hydrolytic deamination of adenosine residues in mRNAs. By changing adenosine to inosine, which is read by the ribosome as guanosine, codons can be mutated and protein structure and function changed. Although adenosine deamination occurs in the nervous system of all metazoans, its biological significance is poorly understood. In mammals, relatively few mRNA substrates for A to I editing have been identified, most encoding proteins involved in excitability. These editing events, however, are absolutely critical for survival. Recent investigations have identified a surprisingly large number of edited 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 both cephalopods and mammals and specifically focuses on voltage dependent K+ channels, the Na+/K+ ATPase and double-stranded RNA specific adenosine deaminase, an editing enzyme. Molecular biological and biochemical approaches are used to examine which codons are modified and how the editing process is regulated. Electrophysiological approaches are used to understand how changes made by editing affect channel and transporter function. These data are important because they provide insight on how A to I editing influences the evolution of nervous function.

C Colina, JJC Rosenthal, JA DeGiorgis, D Srikumar, N Iruku, and M. Holmgren (2007). Structural basis of Na+/K+-ATPase adaptation to marine environments. Nature Struct. and Mol. Biol. In press.

LP Keegan, JJ Rosenthal, LM Roberson, and MA OConnell (2007). Purification and assay of ADAR activity. In Methods in Enzymology: RNA Editing and Modification. Editor: Jonatha Gott. Elsevier. In press.

LM Roberson, and JJ Rosenthal. (2006). An accurate fluorescent assay for quantifying the extent of RNA editing. RNA. 12:1907-1912.

I Soto, J Rosenthal, J Blagburn, and RE Blanco (2006). Fibroblast growth factor 2 applied to the optic nerve after axotomy increases BDNF and TrkB in ganglion cells by activating the ERK and PKA signaling pathways. J. Neurochem. 96: 82-95.

Markaida, U., Rosenthal, J.J.C. and Gilly, W.F. (2005). Tagging studies of the Humboldt squid, Dosidicus gigas, in the Gulf of California , Mexico. Fishery Bulletin. 103:219-226.

T. Bhalla, JJC Rosenthal, M. Holmgren and R. Reenan. (2004) Control of human potassium channel inactivation by editing of a small mRNA hairpin. Nature Struct. Mol. Biol. 2004 11: 950-6.

JJC Rosenthal and W.F. Gilly. (2003) Identified Ion Channels in the Squid Nervous System. Neurosignals. 12: 126-141.

JJC Rosenthal and F. Bezanilla. (2002) Extensive editing of mRNAs for the squid delayed rectifier K+ channel regulates subunit tetramerization. Neuron. 34: 743-757.

JJC Rosenthal and F. Bezanilla. (2002) A comparison of propagated action potentials from tropical and temperate squid axons: different durations and conduction velocities correlate with ionic conductance levels. J. Exp. Biol. 205: 1819-1830.

TI Liu, ZN Lebaric, JJC Rosenthal, and WF Gilly. (2001) Natural substitutions at highly conserved T1-domain residues perturb processing and functional expression of squid Kv1 channels. J. Neurophys. 85: 61-71.