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academies
J Pharmacol Ther Res 2017 Volume 1 Issue 2
November 02-03, 2017 Chicago, USA
4
th
International Congress on
International Conference and Exhibition on
Drug Discovery, Designing and Development
Biochemistry, Molecular Biology: R&D
&
Neuron-specific regulation of alternative pre-mRNA splicing
Sika Zheng
University of California, Riverside, USA
F
amilies of alternative splicing regulators often contain
multiple paralogs presumed to fulfill different functions.
Polypyrimidine tract binding proteins
Ptbp1
and
Ptbp2
exhibit
dynamic stage-specific expression and program developmental
pre-mRNA splicing inneurons, but howandwhy their regulatory
actionsdiffer arenotunderstood. Tocompare their targeting,we
generated a knockin mouse allele that conditionally expresses
Ptbp1
. Bred to a
Ptbp2
knockout, the transgene allowed us to
compare the developmental andmolecular phenotypes of mice
expressing only
Ptbp1
, only
Ptbp2
, or neither protein in the
brain. This knockin
Ptbp1
rescued a forebrain-specific, but not a
pan-neuronal,
Ptbp2
knockout, demonstrating both redundant
and distinct roles for the proteins. Using comprehensive
approaches of biochemistry, RNA-Seq, and CLIP-Seq to probe
their targeting and protein-RNA interactions, we found that
many developmentally regulated exons exhibited different
sensitivities to
Ptbp1
and
Ptbp2
. Nevertheless, the two paralogs
displayed similar RNA binding across the transcriptome,
indicating that their differential targeting does not derive from
their RNA interactions, but from possible different cofactor
interactions.
Speaker Biography
Sika Zheng is an expert in studying RNA binding proteins and alternative splicing. His
lab combines Biochemistry, Molecular Biology, Cell Biology, Neurobiology, Genetics,
Genomics, and Computational Biology to understand the activity, mechanism, function
and dysfunction of gene regulation at the RNA level in the nervous system focusing on
Ptbp1
and
Ptbp2
two RNA binding proteins programming neuron-specific alternative
splicing. He has made seminal contributions revealing the roles of alternative splicing
for neuronal development and the mechanisms of
Ptbp1
/2 controlling neuron-specific
alternative splicing events.
e:
sika.zheng@ucr.edu