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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.