SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

T U M O R C E L L B I O L O G Y P R O G R A M
long introns using the dystrophin (DMD) gene.
Many cases of Duchenne muscular dystrophy
are caused by splicing defects of the DMD gene
transcript.
The high prevalence of clinically relevant
mutations that affect splicing in genetic diseases
and cancer has become increasingly apparent.
The aberrant splicing patterns of many genes are
involved in the establishment or maintenance of
the transformed phenotype or in the progression
to malignancy of cancer cells. Thus, Dr. Mayeda’s
research will advance the basic understanding of
the regulation of pre-mRNA splicing, which will
undoubtedly have a long-term impact on public
human health.
SELECTED PUBLICATIONS
2002
Hou, VC, Lersch, R, Gee, SL, Ponthier, JL, Lo,
AJ, Wu, M, Turck, CW, Koury, M, Krainer, AR,
Mayeda, A, and Conboy, JG. Decrease in
hnRNP A/B expression during erythropoiesis
mediates a pre-mRNA splicing switch. EMBO
Journal 21:6195-204, 2002.
2003
Liu, X, Mayeda, A, Tao, M, and Zheng, Z-M.
Exonic splicing enhancer-dependent selection of
bovine papillomavirus type 1 nucleotide 3225 3’
splice site can be rescued in a cell lacking splicing
factor ASF/SF2 through activation of the
phosphatidylinositol 3-kinase/Akt pathway. Journal
of Virology 77:2105–15, 2003.
Domsic, JK, Wang, Y, Mayeda, A, Krainer, AR,
and Stoltzfus, CM. HIV-1 hnRNP A/B-dependent
exonic splicing silencer ESSV antagonizes
binding of U2AF65 to viral polypyrimidine
tracts. Molecular and Cellular Biology 23:8762-
72, 2003.
Hu, D, Mayeda, A, Trembley, JH, Lahti, JM, and
Kidd, VJ. CDK11 complexes promote premRNA
splicing. Journal of Biological Chemistry
278:8623–29, 2003.
Manabe, T, Katayama, T, Sato, N, Gomi, F,
Hitomi, J, Yanagida, T, Kudo, T, Honda, A,
Mori, Y, Matsuzaki, S, Imaizumi, K, Mayeda, A,
and Tohyama, M. Induced HMGAIa expression
causes aberrant splicing of presenilin-2 premRNA
in sporadic Alzheimer’s disease. Cell
Death and Differentiation 10:698–708, 2003.
Amada, N, Tezuka, T, Mayeda, A, Araki, K,
Takei, N, Todokoro, K, and Nawa, H. A novel
rat orthologue and homologue for the Drosophila
crooked neck gene in neural stem cells and their
immediate descendants. Journal of Biochemistry
135:615–623, 2003.
HIGHLIGHTS/DISCOVERIES
• Demonstrated that splicing activator RNPS1 is
incorporated in the early splicing complex,
stimulates formation of the ATP-dependent
splicing complex, and subsequently increases
generation of both intermediate and final
spliced products.
• Discovered experimental evidence supporting a
novel mechanism, termed ‘nested intron splicing’,
i.e., multiple splicing of internal nested
introns preceding the eventual splicing at the
authentic 5’ and 3’ splice sites by using the human
DMD gene.
CARLOS T. MORAES, PH.D.
Associate Professor of Neurology
DESCRIPTION OF RESEARCH
Although mitochondrial genetics of yeast and
trypanosomes has been explored extensively
in the last 20 years, the study of human mitochondrial
DNA (mtDNA) gained momentum in
1988 with the discovery of diseases associated
with mtDNA mutations. The human mtDNA is
a compact circular genome (16.6 kb) coding for
components of the ATP-producing oxidative
phosphorylation system. Because mtDNA-coded
polypeptides are synthesized in mitochondrialspecific
ribosomes, the mtDNA also codes for a
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 89