The TAR-DNA-binding protein-43 (TDP-43) was initially identified to be a host-cell protein capable of binding the TAR DNA of HIV and repressing transcription. TDP-43 belongs to a group of human RNA-binding proteins with prion-like domains incorporating low complexity sequences. The RNA-binding ability of TDP-43 is conferred by two RNA recognition motifs, while the C-terminal prion-like glycine-rich region mediates protein-protein interactions. One key feature of TDP-43 is its functional involvement in forming cellular granules containing both RNA-binding proteins (RBPs) and nucleic acids. TDP-43 is recruited to these cytoplasmic RNA granules (stress granules, SGs) following exposure to various environmental stresses (oxidative, osmotic, heat shock, viral infection). SGs follow a linear dynamic featuring an initial nucleation/formation followed by assembly into larger structures, and eventual disassembly as the cell recovers. In transformed cell lines, depletion of TDP-43 has a negative impact on each of these steps, indicating a key role for TDP-43 in the regulation of this essential cell survival mechanism (PMID:29765078, PMID:29555476).
Literature supporting the
LLPS: 22579281, 22454397, 27545621, 28112502, 28988034, 29511089, 29438978, 28265061, 30814253, 30728452, 30826182, 30853299, 30100264, 29555476
Functional class of membraneless organelle:
activation/nucleation/signal amplification/bioreactor; protective storage/reservoir; sensor