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We employ mouse (mus musculus) as the primary
model organism for our investigations. Moreover,
it has been reported that amongst all the tissues,
the central nervous system has the highest amount
alternatively spliced transcripts. Thus, we employ
the neural retinal to elucidate the role of Alternative
Splicing in neural development.
Our current work has focused on the role of alternative
splicing in regulating bHLH transcription
factors during retinal development. Specifically,
we have investigated the post-transcriptional regulation
of one of the atonal homologues called
Math5. We have found that this gene is a single
exon gene, which is alternatively spliced to produce
two isoforms. Interestingly, the major isoform is
spliced such that the entire coding sequence is
spliced out. Consequently, most of the RNA that
is produced for Math5 cannot produce a functional
protein. This raises several interesting questions,
which will be the focus of our future investigations.
First, why should retinal progenitor cells produce
Math5-mRNA that does not code for protein
Second, does the non-coding isoform of Math5
have a function Third, is this form of regulation
found in other bHLH transcription factors
Selected Publications
Kanadia, R. N. and C. L Cepko. (2010). Alternative splicing
produces high levels of noncoding isoforms of bHLH transcription
factors during development. Genes and Development 24(3):
229-34
Kanadia,R. N., V. E. Clark, C. Punzo, J. Trimarchi and C. Cepko.
(2008). Temporal requirement of the alternative splicing factor
Sfrs1 for the survival of retinal neurons. Development 135(23):
3923-33.
Kanadia, R. N., J. Shin, Y. Yuan, S. G. Beattie, T. Wheeler, C.
A. Thornton and M. S. Swanson. (2006). Reversal of RNA missplicing
and myotonia following muscleblind overexpression in a
mouse poly(CUG) model for myotonic dystrophy. Proceedings of
the National Academy of Sciences, USA. August 1st; 103 (31):
11748-53.
Kanadia R. N., K. A. Johnstone, A. Mankodi, C. Lungu, C.
A. Thornton, D. Esson D, Timmers, W. W. Hauswirth, M. S.
Swanson. (2003). A muscleblind knockout model for myotonic
dystrophy. Science 302(5652): 1978-80
Kanadia, R. N., Y. Yuan, M. G. Poulos and M. Swanson.
(2005). Journal of Biomolecular Structure and Dynamics, Book
of Abstract Albany 22(6)
Lin, X., J.W. Miller, A. Mankodi, R. N. Kanadia, Y. Yuan, R.
T. Moxley, M. S. Swanson, C. A. Thornton. (2006). Failure of
MBNL1-dependent postnatal splicing transitions in myotonic
dystrophy. Human Molecular Genetics 15 (13): 2087-97.
Y. Yuan, R. N. Kanadia, M. S. Swanson. (2005). Impact
of Unstable Microsatellites on RNA processing (Review).
CHEMTRACTS Biochemistry and Molecular Biology 18(3):
129-140.
Kanadia, R. N., C. R. Urbinati, V. J. Crusselle, D. Luo, Y. J. Lee,
J. K. Harrison, S. P. Oh, M.S. Swanson. (2003). Developmental
expression of mouse muscleblind genes Mbnl1, Mbnl2 and
Mbnl3. Gene Expr Patterns 3(4): 459-62.