Details

Autor(en) / Beteiligte

• Katahira, Masato

Titel

FUS Aggregation by Shear Stress on Pipetting and Its Suppression by Non-coding RNA

Ist Teil von

• Phase Separation in Living Cells, p.3-19

Ort / Verlag

Singapore: Springer Nature Singapore

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Fused in sarcoma/translocated in liposarcoma (FUS/TLS) is a multitasking RNA/DNA-binding protein. FUS aggregation is implicated in various neurodegenerative diseases. We revealed the large conformational change of FUS from a compact to an extended structure upon binding of non-coding RNA transcribed from the upstream region of the cyclin D1 gene. In the course of this study, we found by chance that FUS transforms into the amorphous aggregation state as an instant response to the shear stress caused by usual pipetting even at a low FUS concentration, 100 nM. It was also revealed that the non-coding RNA can suppress the transformation of FUS into aggregates. A small fragment (13 nucleotides) of the full length non-coding RNA (602 nucleotides) was shown to be functional for both the conformational change of FUS and suppression of the transformation of FUS into aggregates. The suppressive effect of RNA on FUS aggregation turns out to be sequence-dependent. These results suggested that the non-coding RNA could be a prospective suppressor of FUS aggregation caused by mechanistic stress in cells. Our finding might pave the way for more research on the role of RNAs as aggregation inhibitors, which could facilitate the development of therapies for neurodegenerative diseases.