Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT

Matías Blaustein; Federico Pelisch; Tamara Tanos; Manuel J Muñoz; Diego Wengier; Leandro Quadrana; Jeremy R Sanford; Jorge P Muschietti; Alberto R Kornblihtt; Javier F Cáceres; Omar A Coso; Anabella Srebrow

doi:10.1038/nsmb1020

Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT

Matías Blaustein, Federico Pelisch, Tamara Tanos, Manuel J Muñoz, Diego Wengier, Leandro Quadrana, Jeremy R Sanford, Jorge P Muschietti, Alberto R Kornblihtt, Javier F Cáceres, Omar A Coso, Anabella Srebrow

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Serine/arginine-rich (SR) proteins are important regulators of mRNA splicing. Several postsplicing activities have been described for a subset of shuttling SR proteins, including regulation of mRNA export and translation. Using the fibronectin gene to study the links between signal-transduction pathways and SR protein activity, we show that growth factors not only modify the alternative splicing pattern of the fibronectin gene but also alter translation of reporter messenger RNAs in an SR protein-dependent fashion, providing two coregulated levels of isoform-specific amplification. These effects are inhibited by specific small interfering RNAs against SR proteins and are mediated by the AKT kinase, which elicits opposite effects to those evoked by overexpressing SR protein kinases Clk and SRPK. These results show how SR protein activity is modified in response to extracellular stimulation, leading to a concerted regulation of splicing and translation.

Original language	English
Pages (from-to)	1037-44
Number of pages	8
Journal	Nature Structural & Molecular Biology
Volume	12
Issue number	12
DOIs	https://doi.org/10.1038/nsmb1020
Publication status	Published - Dec 2005

Keywords / Materials (for Non-textual outputs)

Amino Acid Sequence
Animals
Cell Nucleus
Cytoplasm
Fibronectins
Growth Substances
Humans
Molecular Sequence Data
Nuclear Proteins
Phosphatidylinositol 3-Kinases
Phosphoproteins
Protein Biosynthesis
Proto-Oncogene Proteins c-akt
RNA Splicing
RNA, Messenger
RNA, Small Interfering
RNA-Binding Proteins
Signal Transduction

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10.1038/nsmb1020

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@article{6af60edfdbf2472e8610afa6533c0ea4,

title = "Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT",

abstract = "Serine/arginine-rich (SR) proteins are important regulators of mRNA splicing. Several postsplicing activities have been described for a subset of shuttling SR proteins, including regulation of mRNA export and translation. Using the fibronectin gene to study the links between signal-transduction pathways and SR protein activity, we show that growth factors not only modify the alternative splicing pattern of the fibronectin gene but also alter translation of reporter messenger RNAs in an SR protein-dependent fashion, providing two coregulated levels of isoform-specific amplification. These effects are inhibited by specific small interfering RNAs against SR proteins and are mediated by the AKT kinase, which elicits opposite effects to those evoked by overexpressing SR protein kinases Clk and SRPK. These results show how SR protein activity is modified in response to extracellular stimulation, leading to a concerted regulation of splicing and translation.",

keywords = "Amino Acid Sequence, Animals, Cell Nucleus, Cytoplasm, Fibronectins, Growth Substances, Humans, Molecular Sequence Data, Nuclear Proteins, Phosphatidylinositol 3-Kinases, Phosphoproteins, Protein Biosynthesis, Proto-Oncogene Proteins c-akt, RNA Splicing, RNA, Messenger, RNA, Small Interfering, RNA-Binding Proteins, Signal Transduction",

author = "Mat{\'i}as Blaustein and Federico Pelisch and Tamara Tanos and Mu{\~n}oz, {Manuel J} and Diego Wengier and Leandro Quadrana and Sanford, {Jeremy R} and Muschietti, {Jorge P} and Kornblihtt, {Alberto R} and C{\'a}ceres, {Javier F} and Coso, {Omar A} and Anabella Srebrow",

year = "2005",

month = dec,

doi = "10.1038/nsmb1020",

language = "English",

volume = "12",

pages = "1037--44",

journal = "Nature Structural & Molecular Biology",

issn = "1545-9993",

publisher = "Nature Publishing Group",

number = "12",

}

TY - JOUR

T1 - Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT

AU - Blaustein, Matías

AU - Pelisch, Federico

AU - Tanos, Tamara

AU - Muñoz, Manuel J

AU - Wengier, Diego

AU - Quadrana, Leandro

AU - Sanford, Jeremy R

AU - Muschietti, Jorge P

AU - Kornblihtt, Alberto R

AU - Cáceres, Javier F

AU - Coso, Omar A

AU - Srebrow, Anabella

PY - 2005/12

Y1 - 2005/12

N2 - Serine/arginine-rich (SR) proteins are important regulators of mRNA splicing. Several postsplicing activities have been described for a subset of shuttling SR proteins, including regulation of mRNA export and translation. Using the fibronectin gene to study the links between signal-transduction pathways and SR protein activity, we show that growth factors not only modify the alternative splicing pattern of the fibronectin gene but also alter translation of reporter messenger RNAs in an SR protein-dependent fashion, providing two coregulated levels of isoform-specific amplification. These effects are inhibited by specific small interfering RNAs against SR proteins and are mediated by the AKT kinase, which elicits opposite effects to those evoked by overexpressing SR protein kinases Clk and SRPK. These results show how SR protein activity is modified in response to extracellular stimulation, leading to a concerted regulation of splicing and translation.

AB - Serine/arginine-rich (SR) proteins are important regulators of mRNA splicing. Several postsplicing activities have been described for a subset of shuttling SR proteins, including regulation of mRNA export and translation. Using the fibronectin gene to study the links between signal-transduction pathways and SR protein activity, we show that growth factors not only modify the alternative splicing pattern of the fibronectin gene but also alter translation of reporter messenger RNAs in an SR protein-dependent fashion, providing two coregulated levels of isoform-specific amplification. These effects are inhibited by specific small interfering RNAs against SR proteins and are mediated by the AKT kinase, which elicits opposite effects to those evoked by overexpressing SR protein kinases Clk and SRPK. These results show how SR protein activity is modified in response to extracellular stimulation, leading to a concerted regulation of splicing and translation.

KW - Amino Acid Sequence

KW - Animals

KW - Cell Nucleus

KW - Cytoplasm

KW - Fibronectins

KW - Growth Substances

KW - Humans

KW - Molecular Sequence Data

KW - Nuclear Proteins

KW - Phosphatidylinositol 3-Kinases

KW - Phosphoproteins

KW - Protein Biosynthesis

KW - Proto-Oncogene Proteins c-akt

KW - RNA Splicing

KW - RNA, Messenger

KW - RNA, Small Interfering

KW - RNA-Binding Proteins

KW - Signal Transduction

U2 - 10.1038/nsmb1020

DO - 10.1038/nsmb1020

M3 - Article

C2 - 16299516

SN - 1545-9993

VL - 12

SP - 1037

EP - 1044

JO - Nature Structural & Molecular Biology

JF - Nature Structural & Molecular Biology

IS - 12

ER -

Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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