Redirecting SR Protein Nuclear Trafficking through an Allosteric Platform

被引：20

作者：

Aubol, Brandon E. ^{[1
]}

Hailey, Kendra L. ^{[2
]}

Fattet, Laurent ^{[1
]}

Jennings, Patricia A. ^{[2
]}

Adams, Joseph A. ^{[1
]}

机构：

[1] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2017年 / 429卷 / 14期

关键词：

kinase; kinetics; phosphorylation; phosphatase; SR protein; PRE-MESSENGER-RNA; SPLICING FACTOR ASF/SF2; CATALYTIC SUBUNIT; STRUCTURAL BASIS; PHOSPHATASE; PROCESSIVE PHOSPHORYLATION; RECOGNITION MOTIF; KINETIC-ANALYSIS; DOCKING MOTIF; SERINE-RICH;

D O I：

10.1016/j.jmb.2017.05.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Although phosphorylation directs serine-arginine (SR) proteins from nuclear storage speckles to the nucleoplasm for splicing function, dephosphorylation paradoxically induces similar movement, raising the question of how such chemical modifications are balanced in these essential splicing factors. In this new study, we investigated the interaction of protein phosphatase 1 (PP1) with the SR protein splicing factor (SRSF1) to understand the foundation of these opposing effects in the nucleus. We found that RNA recognition motif 1 (RRM1) in SRSF1 binds PP1 and represses its catalytic function through an allosteric mechanism. Disruption of RRM1-PP1 interactions reduces the phosphorylation status of the RS domain in vitro and in cells, redirecting SRSF1 in the nucleus. The data imply that an allosteric SR protein-phosphatase platform balances phosphorylation levels in a "goldilocks" region for the proper subnuclear storage of an SR protein splicing factor. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：2178 / 2191

页数：14

共 67 条

[1] Processive phosphorylation of alternative splicing factor/splicing factor 2 [J].

Aubol, BE ;

Chakrabarti, S ;

Ngo, J ;

Shaffer, J ;

Nolen, B ;

Fu, XD ;

Ghosh, G ;

Adams, JA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (22) :12601-12606

[2] Release of SR Proteins from CLK1 by SRPK1: A Symbiotic Kinase System for Phosphorylation Control of Pre-mRNA Splicing [J].

Aubol, Brandon E. ;

Wu, Guowei ;

Keshwani, Malik M. ;

Movassat, Maliheh ;

Fattet, Laurent ;

Hertel, Klemens J. ;

Fu, Xiang-Dong ;

Adams, Joseph A. .

MOLECULAR CELL, 2016, 63 (02) :218-228

[3] N-terminus of the protein kinase CLK1 induces SR protein hyperphosphorylation [J].

Aubol, Brandon E. ;

Plocinik, Ryan M. ;

Keshwani, Malik M. ;

McGlone, Maria L. ;

Hagopian, Jonathan C. ;

Ghosh, Gourisankar ;

Fu, Xiang-Dong ;

Adams, Joseph A. .

BIOCHEMICAL JOURNAL, 2014, 462 :143-152

[4] The structure and mechanism of protein phosphatases: Insights into catalysis and regulation [J].

Barford, D ;

Das, AK ;

Egloff, MP .

ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 1998, 27 :133-164

[5] The extended PP1 toolkit: designed to create specificity [J].

Bollen, Mathieu ;

Peti, Wolfgang ;

Ragusa, Michael J. ;

Beullens, Monique .

TRENDS IN BIOCHEMICAL SCIENCES, 2010, 35 (08) :450-458

[6] Hypophosphorylated SR splicing factors transiently localize around active nucleolar organizing regions in telophase daughter nuclei [J].

Bubulya, PA ;

Prasanth, KV ;

Deerinck, TJ ;

Gerlich, D ;

Beaudouin, J ;

Ellisman, MH ;

Ellenberg, J ;

Spector, DL .

JOURNAL OF CELL BIOLOGY, 2004, 167 (01) :51-63

[7] Interaction between the RNA binding domains of Ser-Arg splicing factor 1 and U1-70K snRNP protein determines early spliceosome assembly [J].

Cho, Suhyung ;

Hoang, Amy ;

Sinha, Rahul ;

Zhong, Xiang-Yang ;

Fu, Xiang-Dong ;

Krainer, Adrian R. ;

Ghosh, Gourisankar .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (20) :8233-8238

[8] The role of protein phosphorylation in human health and disease - Delivered on June 30th 2001 at the FEBS Meeting in Lisbon [J].

Cohen, P .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 2001, 268 (19) :5001-5010

[9] The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution [J].

Colwill, K ;

Pawson, T ;

Andrews, B ;

Prasad, J ;

Manley, JL ;

Bell, JC ;

Duncan, PI .

EMBO JOURNAL, 1996, 15 (02) :265-275

[10] SRPK1 and Clk/Sty protein kinases show distinct substrate specificities for serine/arginine-rich splicing factors [J].

Colwill, K ;

Feng, LL ;

Yeakley, JM ;

Gish, GD ;

Caceres, JF ;

Pawson, T ;

Fu, XD .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (40) :24569-24575

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