Single-Cell Biophysics: Measurement, Modulation, and Modeling
Poster Abstracts
53
17-POS
Board 9
A Single-Molecule Approach to Study the Dendritic Function of the Rna-Binding Protein
Tdp-43
Jen-Fei Chu
, Pritha Majumder, Biswanath Chatterjee, Che-Kun James Shen.
Academia Sinica, Taipei, Taiwan.
The RNA-binding protein TDP-43 regulates RNA metabolism at multiple levels, including
transcription, RNA splicing, and microRNA metabolism, as well as a major component of the
cytoplasmic inclusions characteristic of amyotrophic lateral sclerosis and some types of
frontotemporal lobar degeneration. We previously found that TDP-43 represses the translation
initiation of Rac1 mRNAs through binding of TDP-43 to mRNA(s) at specific UG/GU
sequences and consequently the hippocampal spinogenesis. However, direct evidence that TDP-
43 regulates Rac1 mRNAs in spatiotemporal manner has not been documented. We here
conducted a multi-color localization based super-resolution microscopic and single particle
tracking methods at the endogenous level to dissect the interaction of TDP-43 proteins and Rac1
mRNAs in live hippocampal neurons. It would allow us to extract messenger ribonucleoproteins
(mRNPs) information that remains unclear about the TDP-43 protein-Rac1 mRNA complex in
situ. This sheds new light on the pathology of mechanistic pathways induced by mis-metabolism
of TDP-43 protein.