Dr. Joshua J. Rosenthal
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 examines 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. Projects in my lab focus on two general areas. First, we are trying to manipulate the molecular machinery for RNA editing so that we can direct it to edit where we want. Using this approach we can correct genetic mutations and manipulate protein function at the mRNA level. Some of our recent studies have focused on correcting mutations within CFTR, a chloride channel that, when defective, causes cystic fibrosis. A second avenue of investigation in my lab is directed towards better understanding high-level RNA editing in cephalopods. Squid and octopus edit at unprecedented levels and we want to better understand the structure and function of their RNA editing enzymes, and the physiological consequences of the edits on ion channel and transporter function. We are particularly interested in understanding the interaction between RNA editing and the external environment.
Work in my lab is highly integrative. Student projects combine molecular biology, biochemistry and electrophysiology to answer questions that are essentially biological. Very recently we have been investing in next generation sequencing and bioinformatics in order to further expand our approaches.
1R01NS64259-1A2 (PI) Pending. Received a score of 20 (2%)
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.
1R0111223855 (Co-PI) 10/13-10/18
NIH-Director’s Initiative Transformative Research Awards
Site-Directed RNA Editing: a New Method to Correct Genetic Mutations
NS039405-06 (PI) 1/05-12/10
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.
IBN-0344070 (PI) 5/04-5/08
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
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
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.
M. Montiel-Gonzalez, I. Vallecillo, G. Yudowski, and J.J.C. Rosenthal (2013). Correction of mutations within the cystic fibrosis transmembrane conductance regulator by site-directed RNA editing. PNAS (in press).
M. Holmgren, and J.J.C. Rosenthal (2012). Regulation of ion channel and transporter function through RNA editing. In: RNA Editing: Current Research and Future Trends (ed. S. Maas). Caister Academic Press, Essex, U.K. In Press.
C.B. Albertin, L. Bonnaud, C.T. Brown, W.J. Crookes-Goodson, R. R. da Fonseca, C. Di Cristo, B. P. Dilkes, E. Edsinger-Gonzales, R. J. Freeman, Jr., R. T., Hanlon, K. M. Koenig, A. R. Lindgren, M. Q. Martindale, P. Minx, L. L. Moroz, M.T. Nödl, S. V. Nyholm, A. Ogura, J. R. Pungor, J. J. C. Rosenthal, E. M. Schwarz, S. Shigeno, J. M. Strugnell, T. Wollesen, G. Zhang, C. W. Ragsdale (2012). Cephalopod Genomics: A Plan of Strategies and Organization. Stand. in Genom. Sci.. In Press.
S.C. Garrett and J.J.C. Rosenthal (2012). RNA editing underlies temperature adaptation in K+ channels from polar octopuses. Science. 335: 848-51.
J.P. Palavicini, R.A. Correa-Rojas, and J.J.C. Rosenthal (2012). An extra dsRNA binding domain in a squid RNA editing enzyme confers resistance to a high salt environment. J. Biol. Chem. 287:17754-64.
J.J.C. Rosenthal and P.H. Seeburg (2012). A-to-I RNA Editing: Effects on Proteins Key to Neural Excitability. Neuron. 74:432-9.
A.K. Dymowska,T. Manfredi, J.J. Rosenthal JJ, and B.A. Seibel. (2012). Temperature compensation of aerobic capacity and performance in the Antarctic pteropod, Clione antarctica, compared to its northern congener, C. limacina. J. Exp. Biol. 215: 3370-8.
S.C. Garrett and J.J.C. Rosenthal (2012). A Role for A-to-I RNA Editing in Temperature Adaptation. Physiology. 27: 362-9. LP.
Keegan, L. McGurk, JP Palavicini, J. Brindle, S. Paro, X. Li, JJC Rosenthal and MA O’Connell (2011). Functional conservation in human and Drosophila of Metazoan ADAR2 involved in RNA editing: loss of ADAR1 in insects. Nucl. Acids Res.. 214: 2164-74.
C. Gonzalez, A. Lopez-Rodriguez, D. Srikumar, J. J.C. Rosenthal and M. Holmgren (2011). Editing human KV1.1 channel mRNAs disrupts binding of the N-terminus tip at the intracellular cavity. Nat. Commun. 2: 436.
G. Galarza-Munoz, S.I. Soto-Morales, M. Holmgren, and J.J.C. Rosenthal (2011). Physiological adaptation of an Antarctic Na+/K+-ATPase to the cold. J. Exp. Biol. 214(Pt 13):2164-74.
J.P. Castillo, D. De Giorgis, D. Basilio, D.C. Gadsby, J.J. Rosenthal, R. Latorre, M. Holmgren, F. Bezanilla (2011). Energy landscapeof the reactions governing the Na+ deeply occluded state of the Na+/K+-ATPase in the giant axon of the Humboldt squid. PNAS. 108:20556-61.
C. Colina, J.P. Palavicini, D. Srikumar, M. Holmgren and J.J.C. Rosenthal (2010). Regulation of Na+/K+ ATPase Transport Velocity by RNA Editing. PLoS Biol. 8: E1000540.
D. Reyes-Colon, N. Vazquez-Ecevedo, N.M. Rivera, S.H. Jezzini, J. Rosenthal, E.A. Ruiz-Rodriguez, D.J. Baro, A.B. Kohn, L.L. Moroz, and M.A. Sosa (2010). Cloning and distribution of a putative octopamine/tyramine receptor in the central nervous sysem of the freshwater prawn Macrobrachium rosenbergii. Brain Res. 1348:42-54.
N. Vazquez-Acevedo, D. Reyes-Colon, E.A. Ruiz-Rodriguez, N.M. Rivera, J. Rosenthal, A.B. Kohn, L.L. Morozn and M.A. Sosa (2009). Cloning and immunoreactivity of the 5-HT1Mac and 5-HT2Mac receptors in the central nervous system of the freshwater prawn Macrobrachium rosenbergii. J. Comp. Neurol. 513:399-416.
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.
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
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.
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.
JJC Rosenthal and WF Gilly (2003). Identified Ion Channels in the Squid Nervous System. Neurosignals. 12: 126-41.
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.
JJC Rosenthal and F. Bezanilla (2000). Seasonal variation in conduction velocity of action potentials in squid giant axons. Biol. Bull.199: 1-9.
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, 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.
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.
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.
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.
Sonia Soto - sonia dot soto at upr.edu
Isabel Vallecillo - ivalle01 at gmail.com
Maria Fernanda Montiel - mafe1983 at gmail.com
Laura Fernández-Alacid - lfa2 at um.es