MLN51 Stimulates the RNA-Helicase Activity of eIF4AIII

被引：42

作者：

Noble, Christian G. ^{[1
]}

Song, Haiwei ^{[1
]}

机构：

[1] Natl Univ Singapore, Inst Mol & Cell Biol, Lab Macromol Struct, Singapore 117548, Singapore

来源：

PLOS ONE | 2007年 / 2卷 / 03期

关键词：

D O I：

10.1371/journal.pone.0000303

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 core of the exon-junction complex consists of Y14, Magoh, MLN51 and eIF4AIII, a DEAD-box RNA helicase. MLN51 stimulates the ATPase activity of eIF4AIII, whilst the Y14-Magoh complex inhibits it. We show that the MLN51-dependent stimulation increases both the affinity of eIF4AIII for ATP and the rate of enzyme turnover; the KM is decreased by an order of magnitude and k(cat) increases 30 fold. Y14-Magoh do inhibit the MLN51-stimulated ATPase activity, but not back to background levels. The ATP-bound form of the eIF4AIII-MLN51 complex has a 100-fold higher affinity for RNA than the unbound form and ATP hydrolysis reduces this affinity. MLN51 stimulates the RNA-helicase activity of eIF4AIII, suggesting that this activity may be functionally important.

引用

页数：5

共 21 条

[1] Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA [J].

Andersen, Christian B. F. ;

Ballut, Lionel ;

Johansen, Jesper S. ;

Chamieh, Hala ;

Nielsen, Klaus H. ;

Oliveira, Cristiano L. P. ;

Pedersen, Jan Skov ;

Seraphin, Bertrand ;

Le Hir, Herve ;

Andersen, Gregers Rom .

SCIENCE, 2006, 313 (5795) :1968-1972

[2] The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity [J].

Ballut, L ;

Marchadier, B ;

Baguet, A ;

Tomasetto, C ;

Séraphin, B ;

Le Hir, H .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2005, 12 (10) :861-869

[3] The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA [J].

Bono, Fulvia ;

Ebert, Judith ;

Lorentzen, Esben ;

Conti, Elena .

CELL, 2006, 126 (04) :713-725

[4] The DEAD-box protein family of RNA helicases [J].

Cordin, O ;

Banroques, J ;

Tanner, NK ;

Linder, P .

GENE, 2006, 367 :17-37

[5] Association of the breast cancer protein MLN51 with the Exon junction complex via its speckle localizer and RNA binding module [J].

Degot, S ;

Le Hir, H ;

Alpy, F ;

Kedinger, V ;

Stoll, I ;

Wendling, C ;

Seraphin, B ;

Rio, MC ;

Tomasetto, C .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (32) :33702-33715

[6] Metastatic Lymph Node 51, a novel nucleo-cytoplasmic protein overexpressed in breast cancer [J].

Degot, S ;

Régnier, CH ;

Wendling, C ;

Chenard, MP ;

Rio, MC ;

Tomasetto, C .

ONCOGENE, 2002, 21 (28) :4422-4434

[7] Translation is required to remove Y14 from mRNAs in the cytoplasm [J].

Dostie, J ;

Dreyfuss, G .

CURRENT BIOLOGY, 2002, 12 (13) :1060-1067

[8] A novel mode of RBD-protein recognition in the Y14-Mago complex [J].

Fribourg, S ;

Gatfield, D ;

Izaurralde, E ;

Conti, E .

NATURE STRUCTURAL BIOLOGY, 2003, 10 (06) :433-439

[9] Structure of the Y14-magoh core of the Exon junction complex [J].

Lau, CK ;

Diem, MD ;

Dreyfuss, G ;

Van Duyne, GD .

CURRENT BIOLOGY, 2003, 13 (11) :933-941

[10] The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions [J].

Le Hir, H ;

Izaurralde, E ;

Maquat, LE ;

Moore, MJ .

EMBO JOURNAL, 2000, 19 (24) :6860-6869

← 1 2 3 →