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Stefan
Maas, Ph.D.
Assistant Professor
Molecular Biology
Click here to view the Maas Lab
website
Research Summary
Our lab is interested in understanding the molecular basis for
the tremendous complexity and diversity of higher organisms. This
complexity is based on the number of different gene products available
for structural, enzymatic and regulatory functions. Recently, whole-genome
sequencing of a diverse set of species from primitive to highly
developed organisms (bacteria, yeast, worm, fly, fish, mouse, human)
has demonstrated that during evolution the number of building blocks
(genes) in genomes, has not increased at the same rate as the observed
organismic complexity (for example: fruit fly 13,000 genes, homo
sapiens ca. 30,000 genes). This unexpected finding underscores the
important role of post-transcriptional and post-translational mechanisms
for the generation of protein diversity.
We are focusing on a recently discovered phenomenon of pre-mRNA
modification, called RNA editing. In general, the term RNA editing
is used to describe the posttranscriptional alteration of gene sequences
by different mechanisms including the deletion, insertion and modification
of nucleotides. Base changes in codons often lead to amino acid
changes and result in alteration of protein function.
In mammals, the modification of adenosines (A) to inosine (I) appears
to be particularly widespread and is known to regulate crucial functional
properties of neurotransmitter receptors in the brain. Since inosine
acts as guanosine during translation it can change the readout of
edited codons. The coexpression of edited and unedited protein variants
in the same cell can increase exponentially the number of gene products
generated from a single gene. A-to-I RNA editing is catalyzed by
the ADAR (adenosine deaminase acting on RNA) family of enzymes and
these proteins recognize a double-stranded RNA structure formed
from exonic and intronic sequences within the substrate molecule.
In addition to the recoding of mRNA information, the modification
of RNAs by ADARs could potentially affect any biological process
that involves sequence- or structure-specific interactions with
RNA.
We use molecular biological, biochemical and genetics approaches
to study how prevalent A-to-I RNA editing is in the transcriptome
and how it is regulated. Furthermore, we investigate the consequences
of misregulation of or deficiency in RNA editing and how it can
contribute to pathophysiological processes.
Recent Publications
Maas, S., Kawahara, Y., Tamburro, K.M., and Nishikura, K. 2006: A-to-I RNA editing and human disease. RNA Biology, 3(1) e1-9. PDF
Listen to the abstract!
Koeris, M., Funke, L., Shrestha, J., Rich. A., and Maas , S. 2005: Modulation of ADAR1 editing activity by Z-RNA in vitro. Nucleic Acids Res., 33 (16): 5362-70. PDF
Athanasiadis, A., D. Placido, S. Maas, B.A. Brown, 2nd, K. Lowenhaupt, and A. Rich , 2005: The crystal structure of the Zbeta domain of the RNA-editing enzyme ADAR1 reveals distinct conserved surfaces among Z-domains . J Mol Biol , 351 (3): 496-507. PDF
Athanasiadis, A., Rich, A., and Maas, S. 2004: Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLoS Biology, 2 (12) e391 PDF
Luciano, D.J., Mirsky, H., Vendetti, N.J., and Maas, S., 2004: RNA editing of a miRNA precursor. RNA,10(8):1174-1177 PDF
Tsibris, J.C.M., Maas, S., Segars, J.H., Nicosia, S.V., Enkemann, S.A., O'Brien, W.F., and Spellacy, W.N. 2003: New potential regulators of uterine leiomyomata from DNA arrays: The ionotropic glutamate receptor GluR2. Biochem Biophys Res Commun, 312, 249-254 PDF
Maas, S., Rich, A., and Nishikura, K., 2003: A-to-I RNA editing: recent news and remaining mysteries. J.Biol.Chem. 278 (3) 1391-4 PDF
Maas, S., Patt, S., Schrey, M., and Rich, A., 2001: Underediting of GluR-B mRNA in malignant gliomas. Proc. Natl. Acad. Sci. 98 (25), 14687-14692 PDF (see also: Editor's choice in Science Dec. 14, 2001 and in MIT TechTalk)
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