Fused in sarcoma/translocated in liposarcoma: A multifunctional DNA/RNA binding protein

2010 ◽  
Vol 42 (9) ◽  
pp. 1408-1411 ◽  
Author(s):  
Shu Yang ◽  
Sadaf T. Warraich ◽  
Garth A. Nicholson ◽  
Ian P. Blair
2013 ◽  
Vol 288 (34) ◽  
pp. 24731-24741 ◽  
Author(s):  
Adam S. Mastrocola ◽  
Sang Hwa Kim ◽  
Anthony T. Trinh ◽  
Lance A. Rodenkirch ◽  
Randal S. Tibbetts

2021 ◽  
Vol 118 (42) ◽  
pp. e2114412118
Author(s):  
Masato Kato ◽  
Steven L. McKnight

The low-complexity (LC) domain of the fused in sarcoma (FUS) RNA binding protein self-associates in a manner causing phase separation from an aqueous environment. Incubation of the FUS LC domain under physiologically normal conditions of salt and pH leads to rapid formation of liquid-like droplets that mature into a gel-like state. Both examples of phase separation have enabled reductionist biochemical assays allowing discovery of an N-terminal region of 57 residues that assembles into a labile, cross-β structure. Here we provide evidence of a nonoverlapping, C-terminal region of the FUS LC domain that also forms specific cross-β interactions. We propose that biologic function of the FUS LC domain may operate via the mutually exclusive use of these N- and C-terminal cross-β cores. Neurodegenerative disease–causing mutations in the FUS LC domain are shown to imbalance the two cross-β cores, offering an unanticipated concept of LC domain function and dysfunction.


2013 ◽  
Vol 203 (5) ◽  
pp. 737-746 ◽  
Author(s):  
Kyota Yasuda ◽  
Huaye Zhang ◽  
David Loiselle ◽  
Timothy Haystead ◽  
Ian G. Macara ◽  
...  

RNA localization pathways direct numerous mRNAs to distinct subcellular regions and affect many physiological processes. In one such pathway the tumor-suppressor protein adenomatous polyposis coli (APC) targets RNAs to cell protrusions, forming APC-containing ribonucleoprotein complexes (APC-RNPs). Here, we show that APC-RNPs associate with the RNA-binding protein Fus/TLS (fused in sarcoma/translocated in liposarcoma). Fus is not required for APC-RNP localization but is required for efficient translation of associated transcripts. Labeling of newly synthesized proteins revealed that Fus promotes translation preferentially within protrusions. Mutations in Fus cause amyotrophic lateral sclerosis (ALS) and the mutant protein forms inclusions that appear to correspond to stress granules. We show that overexpression or mutation of Fus results in formation of granules, which preferentially recruit APC-RNPs. Remarkably, these granules are not translationally silent. Instead, APC-RNP transcripts are translated within cytoplasmic Fus granules. These results unexpectedly show that translation can occur within stress-like granules. Importantly, they identify a new local function for cytoplasmic Fus with implications for ALS pathology.


2007 ◽  
Vol 177 (4S) ◽  
pp. 78-79
Author(s):  
Lioudmila Sitnikova ◽  
Gary Mendese ◽  
Qin Lui ◽  
Bruce A. Woda ◽  
Di Lu ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document