Nonclassical nuclear localization signals mediate nuclear import of CIRBP

被引：52

作者：

Bourgeois, Benjamin ^{[1
]}

Hutten, Saskia ^{[2
]}

Gottschalk, Benjamin ^{[1
]}

Hofweber, Mario ^{[2
,3
]}

Richter, Gesa ^{[1
]}

Sternat, Julia ^{[1
]}

Abou-Ajram, Claudia ^{[2
]}

Goebl, Christoph ^{[1
]}

Leitinger, Gerd ^{[4
]}

Graier, Wolfgang F. ^{[1
,5
]}

Dormann, Dorothee ^{[2
,3
,6
]}

Madl, Tobias ^{[1
,5
]}

机构：

[1] Med Univ Graz, Gottfried Schatz Res Ctr Cell Signaling Metab &, A-8010 Graz, Austria

[2] Ludwig Maximilians Univ Munchen, BBioMed Ctr, Cell Biol, D-82152 Planegg Martinsried, Germany

[3] Grad Sch System Neurosci, D-82152 Planegg Martinsried, Germany

[4] Med Univ Graz, Div Cell Biol Histol & Embryol, Gottfried Schatz Res Ctr Cell Signaling Metab & A, A-8010 Graz, Austria

[5] BioTechMed Graz, A-8010 Graz, Austria

[6] Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2020年 / 117卷 / 15期

基金：

奥地利科学基金会;

关键词：

CIRBP; Transportin-1; Transportin-3; nuclear import; phase separation; RNA-BINDING PROTEIN; INTRINSICALLY DISORDERED PROTEINS; PHASE-SEPARATION; ARGININE METHYLATION; STRESS GRANULES; INDUCED APOPTOSIS; SPLICING FACTORS; STRUCTURAL BASIS; PY-NLS; FUS;

D O I：

10.1073/pnas.1918944117

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The specific interaction of importins with nuclear localization signals (NLSs) of cargo proteins not only mediates nuclear import but also, prevents their aberrant phase separation and stress granule recruitment in the cytoplasm. The importin Transportin-1 (TNPO1) plays a key role in the (patho-)physiology of both processes. Here, we report that both TNPO1 and Transportin-3 (TNPO3) recognize two nonclassical NLSs within the cold-inducible RNA-binding protein (CIRBP). Our biophysical investigations show that TNPO1 recognizes an arginine-glycine(-glycine) (RG/RGG)-rich region, whereas TNPO3 recognizes a region rich in arginine-serine-tyrosine (RSY) residues. These interactions regulate nuclear localization, phase separation, and stress granule recruitment of CIRBP in cells. The presence of both RG/RGG and RSY regions in numerous other RNA-binding proteins suggests that the interaction of TNPO1 and TNPO3 with these non-classical NLSs may regulate the formation of membraneless organelles and subcellular localization of numerous proteins.

引用

页码：8503 / 8514

页数：12

共 85 条

[1] Methylation of Xenopus CIRP2 regulates its arginine- and glycine-rich region-mediated nucleocytoplasmic distribution [J].