| 000 | 02442nam a2200205Ia 4500 | ||
|---|---|---|---|
| 003 | MX-MdCICY | ||
| 005 | 20251009160707.0 | ||
| 040 | _cCICY | ||
| 090 | _aB-21860 | ||
| 245 | 1 | 0 | _aPhase transition of fibrillarin LC domain regulates localization and protein interaction of fibrillarin |
| 490 | 0 | _aBiochemical Journal, 478(4), 799-810, 2021 | |
| 500 | _aArtículo | ||
| 520 | 3 | _aA key nucleolar protein, fibrillarin, has emerged as an important pharmacological target as its aberrant expression and localization are related to tumorigenesis, chemoresistance and poor survival in breast cancer patients. Fibrillarin contains a N-terminal low complexity sequence (LC) domain with a skewed amino acid distribution, which is known to undergo a phase transition to liquid-like droplets. However, the underlying mechanism of the phase transition of the fibrillarin LC domain and its physiological function are still elusive. In this study, we show that the localization of fibrillarin and its association with RNA binding proteins is regulated by this phase transition. Phenylalanine-to-serine substitutions of the phenylalanine:glycine repeats in the fibrillarin LC domain impede its phase transition into liquid-like droplets, as well as the hydrogel-like state composed of polymers, and also its incorporation into hydrogel or liquid-like droplets composed of wild-type LC domains. When expressed in cultured cells, fibrillarin containing the mutant LC domain fails to localize to the dense fibrillar component of nucleoli in the same way as intact fibrillarin. Moreover, the phase transition of the fibrillarin LC domain is required for the interaction of fibrillarin with other RNA binding proteins, such as FUS, TAF15, DDX5 and DHX9. Taken together, the results suggest that the phenylalanine residues in the LC domain are critical for the phase transition of fibrillarin, which in turn regulates the sub-nucleolar localization of fibrillarin and its interaction with RNA binding proteins, providing a useful framework for regulating the function of fibrillarin. | |
| 650 | 1 | 4 | _aFIBRILLARIN;LC DOMAIN;PHASE TRANSITION;NUCLEOLUS;RNA BINDING PROTEINS |
| 700 | 1 | 2 | _aKim, E. |
| 700 | 1 | 2 | _aKwon, I. |
| 856 | 4 | 0 |
_uhttps://drive.google.com/file/d/1LbLHps8664maCoSsTl_pEmWJSDEmX_0U/view?usp=drive_link _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx |
| 942 |
_2Loc _cREF1 |
||
| 008 | 251009s9999 xx 000 0 und d | ||
| 999 |
_c61950 _d61950 |
||