DYRK1A accumulates in splicing speckles through a novel targeting signal and induces speckle disassembly

Mónica Álvarez, Xavier P. Estivill, Susana de la Luna

Research output: Contribution to journalReview article

91 Citations (Scopus)

Abstract

The protein kinase DYRK1A is distributed throughout the nucleoplasm, accumulating in speckle-like regions. We have found that this punctuated nuclear distribution is determined by the contribution of several elements. Although the nuclear import is mediated by two distinct nuclear localization signals, one at the N-terminus and the other located in the linker region, between subdomains X and XI of the catalytic domain, the accumulation in speckles that are SC35 positive depends on a sequence motif that is located C-terminal to the kinase domain and comprises a histidine tail. A similar sequence is also responsible for the targeting of cyclin T1. Therefore the histidine-rich region represents a novel splicing speckle targeting signal. Moreover, overexpression of DYRK1A induces speckle disassembly. Such disassembly is DYRK1A activity specific, since the overexpression of a DYRK1A kinase inactive mutant, the paralogous DYRK1B or a chimeric protein DYRK1B that has been directed to the speckles via the DYRK1A targeting signal, leaves the SC35 speckle pattern untouched. Thus DYRK1A protein kinase may play a role in regulating the biogenesis of the splicing speckle compartment.

Original languageEnglish
Pages (from-to)3099-3107
Number of pages9
JournalJournal of Cell Science
Volume116
Issue number15
DOIs
Publication statusPublished - 1 Aug 2003
Externally publishedYes

Fingerprint

Histidine
Protein Kinases
Cyclin T
Phosphotransferases
Nuclear Localization Signals
Cell Nucleus Active Transport
Catalytic Domain
Proteins

Keywords

  • Cycling T1
  • DYRK1A
  • Histidine
  • Kinase
  • Speckle disassembly
  • Splicing

ASJC Scopus subject areas

  • Cell Biology

Cite this

DYRK1A accumulates in splicing speckles through a novel targeting signal and induces speckle disassembly. / Álvarez, Mónica; Estivill, Xavier P.; de la Luna, Susana.

In: Journal of Cell Science, Vol. 116, No. 15, 01.08.2003, p. 3099-3107.

Research output: Contribution to journalReview article

@article{36dfd3f030244677880b7e5622ea1780,
title = "DYRK1A accumulates in splicing speckles through a novel targeting signal and induces speckle disassembly",
abstract = "The protein kinase DYRK1A is distributed throughout the nucleoplasm, accumulating in speckle-like regions. We have found that this punctuated nuclear distribution is determined by the contribution of several elements. Although the nuclear import is mediated by two distinct nuclear localization signals, one at the N-terminus and the other located in the linker region, between subdomains X and XI of the catalytic domain, the accumulation in speckles that are SC35 positive depends on a sequence motif that is located C-terminal to the kinase domain and comprises a histidine tail. A similar sequence is also responsible for the targeting of cyclin T1. Therefore the histidine-rich region represents a novel splicing speckle targeting signal. Moreover, overexpression of DYRK1A induces speckle disassembly. Such disassembly is DYRK1A activity specific, since the overexpression of a DYRK1A kinase inactive mutant, the paralogous DYRK1B or a chimeric protein DYRK1B that has been directed to the speckles via the DYRK1A targeting signal, leaves the SC35 speckle pattern untouched. Thus DYRK1A protein kinase may play a role in regulating the biogenesis of the splicing speckle compartment.",
keywords = "Cycling T1, DYRK1A, Histidine, Kinase, Speckle disassembly, Splicing",
author = "M{\'o}nica {\'A}lvarez and Estivill, {Xavier P.} and {de la Luna}, Susana",
year = "2003",
month = "8",
day = "1",
doi = "10.1242/jcs.00618",
language = "English",
volume = "116",
pages = "3099--3107",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "15",

}

TY - JOUR

T1 - DYRK1A accumulates in splicing speckles through a novel targeting signal and induces speckle disassembly

AU - Álvarez, Mónica

AU - Estivill, Xavier P.

AU - de la Luna, Susana

PY - 2003/8/1

Y1 - 2003/8/1

N2 - The protein kinase DYRK1A is distributed throughout the nucleoplasm, accumulating in speckle-like regions. We have found that this punctuated nuclear distribution is determined by the contribution of several elements. Although the nuclear import is mediated by two distinct nuclear localization signals, one at the N-terminus and the other located in the linker region, between subdomains X and XI of the catalytic domain, the accumulation in speckles that are SC35 positive depends on a sequence motif that is located C-terminal to the kinase domain and comprises a histidine tail. A similar sequence is also responsible for the targeting of cyclin T1. Therefore the histidine-rich region represents a novel splicing speckle targeting signal. Moreover, overexpression of DYRK1A induces speckle disassembly. Such disassembly is DYRK1A activity specific, since the overexpression of a DYRK1A kinase inactive mutant, the paralogous DYRK1B or a chimeric protein DYRK1B that has been directed to the speckles via the DYRK1A targeting signal, leaves the SC35 speckle pattern untouched. Thus DYRK1A protein kinase may play a role in regulating the biogenesis of the splicing speckle compartment.

AB - The protein kinase DYRK1A is distributed throughout the nucleoplasm, accumulating in speckle-like regions. We have found that this punctuated nuclear distribution is determined by the contribution of several elements. Although the nuclear import is mediated by two distinct nuclear localization signals, one at the N-terminus and the other located in the linker region, between subdomains X and XI of the catalytic domain, the accumulation in speckles that are SC35 positive depends on a sequence motif that is located C-terminal to the kinase domain and comprises a histidine tail. A similar sequence is also responsible for the targeting of cyclin T1. Therefore the histidine-rich region represents a novel splicing speckle targeting signal. Moreover, overexpression of DYRK1A induces speckle disassembly. Such disassembly is DYRK1A activity specific, since the overexpression of a DYRK1A kinase inactive mutant, the paralogous DYRK1B or a chimeric protein DYRK1B that has been directed to the speckles via the DYRK1A targeting signal, leaves the SC35 speckle pattern untouched. Thus DYRK1A protein kinase may play a role in regulating the biogenesis of the splicing speckle compartment.

KW - Cycling T1

KW - DYRK1A

KW - Histidine

KW - Kinase

KW - Speckle disassembly

KW - Splicing

UR - http://www.scopus.com/inward/record.url?scp=0041885252&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041885252&partnerID=8YFLogxK

U2 - 10.1242/jcs.00618

DO - 10.1242/jcs.00618

M3 - Review article

VL - 116

SP - 3099

EP - 3107

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 15

ER -