Dr. J. Rosenthal
Research Interests
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→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 squid and octopus 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→I editing influences the evolution of nervous function.
| Clione antarctica swimming at 0℃ | Clione limacina swimming at 12℃ |
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Ongoing
1R01NS64259-1A2 (PI) (Pending. Received a score of 20 (2%)).
NINDS R01
Regulation of the Na/K Pump by RNA Editing
The major goals of this work is to assess how RNA editing affects squid Na/K pump function and to use this information to upregulate human Na/K pump activity.
NS039405-06 (PI) 1/05-12/10
NIH-SNRP
Regulation of Na+/K+ ATPase function by RNA editing
The major goal of this work is to map RNA editing in the Na+/K+ ATPase and see how it affects function.
Completed
IBN-0344070 (PI) 5/04-5/08
NSF-IBN
Species-dependent regulation of excitability by RNA editing
The major goal of this work is to see how squid from different thermal environments edit their delayed rectifier K+ channels and to try to understand the differences.
9980360 (Co-PI) 2001 - 2003
NSF
Temperature adaptation in the locomotor system of polar pteropods.
The major goals of this project are to examine the role played by Na+ channel gating, neuromuscular anatomy, response to neurotransmitters and the biomechanics of swimming play in adaptation to cold in polar pteropod molluscs.
GM20314-01 (PI) 2000 - 2001
NIH NRSA-Postdoctoral
Molecular regulation of excitability by RNA editing
The major goals of this project were to understand how editing of a K channel mRNA expressed in the squid giant axon system impacts channel function and action potential repolarization.
- H Goldfine, JJ Rosenthal, and NC Johnston (1987). Lipid shape as a determinant of lipid composition in clostridium butyricum. The effects of incorporation of various fatty acids of the ratios of the major ether lipids. Biochim. Biophys. Acta. 904: 283-9.
- J Rosenthal, and A Diamant (1990). In vitro primary cell cultures from Penaeus semisulcatus. Pathol. Mar. Sci. 1:7-13J.J.C. Rosenthal, and WF Gilly (1993). Amino acid sequence of a putative sodium channel expressed in the giant axon of the squid Loligo opalescens.. Proc. Natl. Acad. Sci. USA. 90:10026-10030.
- WF Gilly, MT Lucero, M Perri, and J Rosenthal (1995). Control of the spatial distribution of sodium channels in the squid giant axon and its cell bodies. In: Cephalopod neurobiology (ed. N.J. Abbott, R. Williamson, and L. Maddock). pp.173-193. Oxford University Press, New York.
- JJC Rosenthal, RG Vickery, and WF Gilly (1996). Molecular identification of SqKv1A: a candidate for the delayed-rectifier K channel in squid giant axon. J. Gen. Physiol. 108:207-219.
- C Mathes, JJC Rosenthal, CM Armstrong, and WF Gilly ( 1997). Fast inactivation of delayed rectifier K conductance in squid giant axon and its cell bodies. J. Gen. Physiol. 109: 1-14.
- JJC Rosenthal, TI Liu, and W.F. Gilly ( 1997). A family of delayed-rectifier Kv1 cDNAs showing cell-type specific expression in the squid stellate ganglion/giant fiber lobe complex. J. Neurosci. 17: 5070-5079.
- JJC Rosenthal and F. Bezanilla (2000). Seasonal variation in conduction velocity of action potentials in squid giant axons. Biol. Bull.199: 1-9.
- 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.
- 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.
- JJC Rosenthal and WF Gilly (2003). Identified Ion Channels in the Squid Nervous System. Neurosignals. 12: 126-41.
- T Bhalla, JJ Rosenthal, M Holmgren, R Reenan (2004). Control of human potassium channel inactivation by editing of a small mRNA hairpin. Nat Struct Mol Biol. 11: 950-956.
- 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.
- LM Roberson, and JJ Rosenthal. (2006). An accurate fluorescent assay for quantifying the extent of RNA editing. RNA. 12:1907-1912.
- LP Keegan, JJ Rosenthal, LM Roberson, and MA O’Connell (2007). Purification and assay of ADAR activity. Methods in Enzymology: RNA Editing and Modification. 424: 301-17
- 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. 14:427-31.
- BA Seibel, A Dymowska, and J Rosenthal (2007). Metabolic temperature compensation and coevolution of locomotory performance in pteropod molluscs. J. Integ. and Comp. Biol. 47:880-91
- JJC Rosenthal, BA Seibel, A Dymowska, and F Bezanilla (2009). Trade-off between aerobic capacity and locomotor capability in an Antarctic pteropod. PNAS.106: 6192-6196.
- JP Palavicini, MA O’Connell, and JJC Rosenthal (2009). An extra double-stranded RNA binding domain confers high activity on a squid RNA editing enzyme. RNA. 15(6):1208-18..
Current Lab Members:
- Sonia Soto (Technician: sonia.soto@upr.edu)
- Gaddiel Galarza (Graduate student: gaddiel.galarza@gmail.com)
- Juan Pablo Palavicini (Graduate student: jppalavicini@gmail.com)
- Rodrigo Correa (Graduate student: rodri.correa@gmail.com)
- Sandra Garrett (Graduate student: sandycoralgarrett@yahoo.com)
- Maria Fernanda Montiel (Graduate student: mafe1983@gmail.com)