Joshua Rosenthal

_dsc7871-sm

Joshua Rosenthal
Senior Scientist
Email Joshua Rosenthal
Phone: (508) 289-7253

Education:
Haverford College, B.A. Biology
Stanford University, Ph.D. Biology

Current Projects:
High level Recoding by RNA editing in Cephalopods
Site-Directed RNA Editing
Marine Model Organism Development
Structural and functional connectivity of squid chromatophores

Job Opportunities:
Postdoctoral Scientist – Rosenthal Lab

Full Publication List

Research Statement: The central dogma of biology is that genetic information passes faithfully from DNA to RNA before being decoded into proteins. This information can be manipulated at any stage. When done in DNA, the changes are irreversible. Organisms often alter information in RNA because it provides a flexible platform. They use diverse tools. One example is RNA editing through adenosine deamination, a process that occurs in all multicellular animals. Unlike alternative splicing, which shuffles relatively large regions of RNA, editing targets single bases. Catalyzed by the ADAR family of enzymes, specific adenosines are converted to inosine at precise positions within RNAs. Although inosine is not one of the four Watson-Crick bases, it is a biological mimic for guanosine during translation. Thus when editing occurs within messenger RNAs, it can recode specific codons, leading to changes to protein structure and function. By recoding mRNAs, organisms gain the option to express a diverse quiver of proteins when and where they choose. My lab focuses on RNA editing. We look at cephalopods because they recode proteins through RNA editing far more often than other organisms. We also are developing ways to redirect RNA editing to sites of our choosing.

Extra nuclear expression of the RNA editing enzyme ADAR in the squid stellate ganglion.
An Octopus vulgaris surveying the reef in Vieques, Puerto Rico. Photo courtesy of Ramiro Artigas.
The most common form of RNA editing in animals is a deamination of adenosine to inosine within RNAs.

Select Publications:

Liscovitch-Brauer, N., Alon, S., Porath, H.T., Elstein, B., Unger, R., Ziv, T., Admon, A., Levanon, E.Y., Rosenthal, J.J.C.*, and Eisenberg, E.* (2017). Trade-off between transcriptome plasticity and genome evolution in cephalopods. Cell. (In press).

M.F. Montiel-Gonzalez, I.C. Vallecillo-Viejo, and J.J.C. Rosenthal (2016). An efficient system for selectively altering genetic information in mRNAs. NAR 44: e157.

S. Alon, S.C. Garrett, E.Y. Levanon, S. Olson, B.R. Graveley, J.J.C. Rosenthal, and E. Eisenberg (2015). The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing. eLife 4: 10.7554/eLife.05198.

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. 110: 18285-90.

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.

S.C. Garrett and J.J.C. Rosenthal (2012). RNA editing underlies temperature adaptation in K+ channels from polar octopuses. Science. 335: 848-51.

Lab Members:

maria-montiel-gonzalezMaria Montiel-González

In recent years, strategies to correct genetic mutations by modifying DNA and RNA molecules have received increasing attention. My project has been based on engineering a site-directed RNA editing strategy to use it as a tool to correct specific mistakes within mRNAs. RNA Editing is an enzymatic process that performs adenosine (A) to inosine (I) changes within RNAs. This process is catalyzed by Adenosine Deaminases that Act on RNA (ADARs). I is structurally similar to guanosine (G), and an A-to-I change is interpreted as an A-to-G change by ribosomes and other biological processes. As a result of this mechanism, protein function may be altered, particularly if editing occurs within mRNA coding regions. In the laboratory we have engineered an “editase” that can direct the editing process to a specific adenosine of our choosing (for a description of our strategy see R. Reenan New Engl J Med 370:172-174). Using this strategy, we have been able to correct a premature termination codon (PTC) mutation in an eGFP fluorescent reporter with a 70% of editing efficiency. At present, we are testing our strategy in several mutations that cause Cystic Fibrosis and can make corrections within cells at efficiencies ranging from 20% to 80%.

yisrael-schnytzerYisrael Schnytzer

I am broadly interested in animal behavior, the underlying driving molecular mechanisms and their evolutionary context. The majority of my work has revolved around the tidal zone. During my MSc I studied the little known association between boxer crabs and the anemones they hold in their claws. This was a “classic” behavioral study, focused on host location, feeding habits and general natural history. Then during my PhD I focused on trying to understand tidal rhythmicity, using a limpet species as the model organism. I integrated both behavioral work in the field and lab, in conjuncture with a large transcriptomic project aimed at identifying potential tidal clock genes. At present I am a post-doc in the Rosenthal lab at MBL in Woods Hole. My work here focuses on the involvement of RNA editing in cephalopod rhythmicity and clock genes. Beside that I am fond of photography and cooking.

isabel-vallecillo-viejoIsabel Vallecillo-Viejo

RNA editing is a universal process used by all metazoans to generate genetic diversity. In our lab, we study the most common form of editing mediated by the hydrolytic deamination of adenosines in RNAs. This process is catalysed by Adenosine Deaminases that Act on RNA (ADARs), a family of enzymes that convert Adenosines to Inosines in RNA. Inosine is a nucleoside that is structurally similar to guanosine and thus an A-to-I change is interpreted as an A-to-G change by the translational machinery. As a result of this mechanism, protein function may be altered as long as editing occurs in mRNA coding regions. From a therapeutic standpoint, RNA editing could be used as a tool in order to alter genetic information and change protein function. My project focuses on optimizing a strategy developed in our lab to manipulate the molecular machinery for RNA editing so that we can direct it to edit where we want. I am also interested in understanding the molecular basis for extensive editing in squid. Bioinformatics data has shown that squid RNA editing is robust, suggesting that there may be mechanistic differences underlying the editing process in this organism. I am currently studying the structure and function of squid RNA editing enzymes.