Dr. Paula Grabowski

Genetics
K. Arndt
T.-L. Ashman
G. Campbell
D. Chapman
G. Hatfull
J. Hildebrand
L. Jacobson
S. Kalisz
J. Martens
W. Saunders
B. Stronach
S. Tonsor
R. Wood

Microbiology
J. Boyle
G. Hatfull
R. Hendrix
J. Lawrence
J. Pipas
M. Popa
R.L. Duda
S. Godfrey
V. Oke

Molecular Biology
K. Arndt
J. Franzen
P. Grabowski
G. Hatfull
R. Hendrix
L. Jen-Jacobson
J. Martens
C. Peebles
J. Pipas
J. Rosenberg
A. Schwacha
C. Walsh

Plant Biology
T.-L. Ashman
W. Carson
S. Kalisz
V. Oke
C. Partanen
S. Tonsor
B. Traw

Science Education
A. Bledsoe
K. Curto
L. Daniels
S. Godfrey
N. Kaufmann
C. LaFave
J. Newman
E. Polinko
M. Popa
L. Roberts
T. Seiflein
R. Sherwin
A. Slinskey Legg

Structural Biology
M. Grabe
J. Hempel
R. Hendrix
L. Jen-Jacobson
J. Rosenberg
A. VanDemark

Former Faculty

Photo of Dr.
Grabowski

Alternative RNA Splicing in the Nervous System

Professor

Dr. Grabowski received her Ph.D. in 1983 with Tom Cech at the University of Colorado, performed her postdoctoral studies with Philip Sharp at the Massachusetts Institute of Technology, and joined the Department in 1991.

Currently, Dr. Grabowski is accepting graduate students in her laboratory. Dr. Grabowski is accepting undergraduate researchers, and does sponsor students in other laboratories.

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of Paula Grabowski

Alternative pre-mRNA splicing generates widespread transcript diversity by specifying the inclusion or exclusion of sequences encoding protein functional domains. We are interested in understanding how these mechanisms are coordinated in the nervous system to tailor the structure of protein molecules for their specific roles at the synapse relating to neuronal communication and plasticity.

The Glutamate NMDA (N-methyl-D-aspartate) receptor plays roles at the synapse that are essential for learning and memory, and we have been using the NR1 subunit of this receptor as a model system to study splicing regulation in the brain. The NI and CI cassette exons of the NR1 subunit pre-mRNA encode protein domains that allow the receptor to respond to extracellular interactions or participate in intracellular signaling.

We have identified an RNA binding protein called NAPOR/CUGBP2, which is enriched in the cognitive areas of the brain, and which has dual properties for silencing and enhancing the NI and CI cassette exons, respectively. We are probing the underlying basis for dual roles of NAPOR/CUGBP2 in this system using a variety of biochemical and genetic approaches. In context, we wish to understand the integrated roles of the full set of factors involved in these mechanisms. We are further extending this work to identify patterns of global coordination of splicing in neurons.

Additional studies in the lab are focused on understanding how splicing decisions can respond to neuronal excitation. We have recently developed a system to study how cell excitation stimulates the skipping of the CI cassette exon in cortical neurons in culture. This effect requires a UAGG silencing motif code within the exon, which implicates hnRNP A1 as a candidate regulatory factor. We are currently using a variety of approaches to tease apart the molecular dialog between the cell membrane and the nucleus that is responsible for the induced splicing changes. The biological rationale for induced splicing changes in neurons is also under investigation.

Publication Archive
49 Citations
35 Abstracts
28 PDFs

Recent Publications of Paula Grabowski

Grabowski, P.J. (2007) RNA-binding proteins switch gears to drive alternative splicing in neurons. Nat. Struct. Mol. Biol. 14:577-579

An, P., and P.J. Grabowski (2007) Exon silencing by UAGG motifs in response to neuronal excitation. PLoS Biol. 5:e36 (PDF Reprint: 2.9 MB)

Grabowski, P.J. (2005) Splicing-active nuclear extracts from rat brain. Methods 37:323-330 (PDF Reprint: 306 kb)

Xu, X.M., H. Mix, B.A. Carlson, P.J. Grabowski, V.N. Gladyshev, M.J. Berry, and D.L... Hatfield (2005) Evidence for direct roles of two additional factors, SECp43 and SLA, in the selenoprotein synthesis machinery. J. Biol. Chem. 280:568-575 (PDF Reprint: 564 kb)

Han, K., G. Yeo, P. An, C.B. Burge, and P.J. Grabowski (2005) A combinatorial code for splicing silencing: UAGG and GGGG motifs. PLoS Biol. 3:e158 (PDF Reprint: 869 kb)

Grabowski, P.J. (2004) A molecular code for splicing silencing: configurations of guanosine-rich motifs. Biochem. Soc. Trans. 32:924-927 (PDF Reprint: 244 kb)

Miné, M., M. Brivet, G. Touati, P. Grabowski, M. Abitbol, and C. Marsac (2003) Splicing error in E1alpha pyruvate dehydrogenase mRNA caused by novel intronic mutation responsible for lactic acidosis and mental retardation. J. Biol. Chem. 278:11768-11772 (PDF Reprint: 235 kb)

Black, D.L., and P.J. Grabowski (2003) Alternative pre-mRNA splicing and neuronal function. Prog. Mol. Subcell. Biol. 31:187-216

Grabowski, P. (2002) Alternative splicing in parallel. Nat. Biotechnol. 20:346-347 (PDF Reprint: 49 kb)

Zhang, W., H. Liu, K. Han, and P.J. Grabowski (2002) Region specific alternative splicing in the nervous system: implications for regulation by the RNA binding protein, NAPOR. RNA 8:671-685 (PDF Reprint: 848 kb)

Wu, J.I., R. Reed, P.J. Grabowski, and K. Artzt (2002) The function of quaking in myelination: Regulation of alternative splicing. Proc. Natl. Acad. Sci., USA 99:4233-4238 (PDF Reprint: 493 kb)

Liu, H., W. Zhang, R. Reed, W. Liu, and P.J. Grabowski (2002) Mutations in RRM4 uncouple the splicing repression and RNA-binding activities of polypyrimidine tract binding protein. RNA 8:137-149 (PDF Reprint: 1.3 MB)

Grabowski, P.J., and D.L. Black (2001) Alternative RNA splicing in the nervous system. Prog. Neurobiol. 65:289-308 (PDF Reprint: 347 kb)

Grabowski, P.J. (2000) Genetic evidence for a Nova regulator of alternative splicing in the brain. Neuron 25:254-256 (PDF Reprint: 47 kb)

How to Contact Paula Grabowski

US Mail
University of Pittsburgh
Department of Biological Sciences
A502A Langley Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone, FAX, Internet
Office : (412) 624-6983
Lab : (412) 624-6984
FAX : (412) 624-4826
Email : pag4+@pitt.edu
Web :

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