Conserved Sr Protein Kinase Functions in Nuclear Import and Its Action Is Counteracted by Arginine Methylation in<i>Saccharomyces cerevisiae</i>

Yun, Chi Young; Fu, Xiang Dong

doi:10.1083/jcb.150.4.707

Cited by 148 publications

(173 citation statements)

References 50 publications

(96 reference statements)

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“…The phosphorylation of the RS elements may inactivate the nuclear localization signal via a masking mechanism [43]. For example, phosphorylation of the most C-terminal SR\RS dipeptide of budding yeast Npl3 by the Sky1 kinase is required for the nuclear import of Npl3 [44]. In addition, Sky1-mediated phosphorylation changes protein interactions and cellular localization of several mammalian SR proteins expressed in budding yeast [45].…”

Section: Discussionmentioning

confidence: 99%

Interactions between two fission yeast serine/arginine-rich proteins and their modulation by phosphorylation

Tang

Käufer

Lin

2002

Biochemical Journal

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The unexpected low number of genes in the human genome has triggered increasing attention to alternative pre-mRNA splicing, and serine\arginine-rich (SR) proteins have been correlated with the complex alternative splicing that is a characteristic of metazoans. SR proteins interact with RNA and splicing protein factors, and they also undergo reversible phosphorylation, thereby regulating constitutive and alternative splicing in mammals and Drosophila. However, it is not clear whether the features of SR proteins and alternative splicing are present in simple and genetically tractable organisms, such as yeasts. In the present study, we show that the SR-like proteins Srp1 and Srp2, found in the fission yeast Schizosaccharomyces pombe, interact with each other and the interaction is modulated by protein phosphorylation. By using Srp1 as bait in a yeast two-hybrid

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Section: Discussionmentioning

confidence: 99%

Interactions between two fission yeast serine/arginine-rich proteins and their modulation by phosphorylation

Tang

Käufer

Lin

2002

Biochemical Journal

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“…Protein methylation has also been shown to control splicing factors or splicing [188,189]. Currently there is no evidence available to support a role for methylation in Ca ++ -regulated alternative splicing.…”

Section: Splicing Factors Regulated By Ca ++ Signalsmentioning

confidence: 99%

Control of alternative pre-mRNA splicing by Ca++ signals

Xie¹

2008

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Alternative pre-mRNA splicing is a common way of gene expression regulation in metazoans. The selective use of specific exons can be modulated in response to various manipulations that alter Ca ++ signals, particularly in neurons. A number of splicing factors have also been found to be controlled by Ca ++ signals. Moreover, pre-mRNA elements have been identified that are essential and sufficient to mediate Ca ++ -regulated splicing, providing model systems for dissecting the involved molecular components. In neurons, this regulation likely contributes to the fine-tuning of neuronal properties.

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“…Previous biochemical characterizations indicate that the SRPK family members possess high affinity for RS domain-containing splicing factors (3,4,31,32), making it possible to prepare a stable kinase-substrate complex for the start-trap strategy described below. We prepared recombinant SRPK1 and ASF͞SF2 and purified them to homogeneity for the current study.…”

Section: Formation Of a Stable Srpk1-asf͞sf2 Complex For Kinetic Studmentioning

confidence: 99%

Processive phosphorylation of alternative splicing factor/splicing factor 2

Aubol

Chakrabarti

Ngo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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131

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SR proteins, named for their multiple arginine͞serine (RS) dipeptide repeats, are critical components of the spliceosome, influencing both constitutive and alternative splicing of pre-mRNA. SR protein function is regulated through phosphorylation of their RS domains by multiple kinases, including a family of evolutionarily conserved SR protein-specific kinases (SRPKs). The SRPK family of kinases is unique in that they are capable of phosphorylating repetitive RS domains with remarkable specificity and efficiency. Here, we carried out kinetic experiments specially developed to investigate how SRPK1 phosphorylates the model human SR protein, ASF͞SF2. By using the start-trap strategy, we monitored the progress curve for ASF͞SF2 phosphorylation in the absence and presence of an inhibitor peptide directed at the active site of SRPK1. ASF͞SF2 modification is not altered when the inhibitor peptide (trap) is added with ATP (start). However, when the trap is added first and allowed to incubate for a specific delay time, the decrease in phosphate content of the enzyme-substrate complex follows a simple exponential decline corresponding to the release rate of SRPK1. These data demonstrate that SRPK1 phosphorylates a specific region within the RS domain of ASF͞SF2 by using a fully processive catalytic mechanism, in which the splicing factor remains ''locked'' onto SRPK1 during RS domain modification.B oth the assembly of the spliceosome and the specificity of splice-site selection in mammalian cells require SR proteins, which contain one or two RNA-recognition motifs (RRMs) in the N terminus and a signature domain enriched with arginine͞ serine dipeptide repeats (RS) in the C terminus (1, 2). The SR proteins are phosphorylated and activated by the SRPK and Clk͞Sty families of protein kinases (3)(4)(5). This posttranslational modification is required for translocation of the SR protein from the cytoplasm to the nucleus (6, 7) and recruitment of the SR proteins from nuclear speckles (also known as splicing-factor compartments) to nascent transcripts for cotranscriptional splicing (8-10). Phosphorylated SR proteins are believed to facilitate 5Ј splice-site recognition through interaction with the RS domain in U1-70 K (a component of the U1 small nuclear ribonucleoprotein) and 3Ј splice-site selection by means of the RS domains present in the U2AF heterodimer (11-13). Finally, reversal of the kinase action by protein phosphatases appears to be essential for spliceosome activation and the return of splicing factors to nuclear speckles (5). ASF͞SF2 is a prototypical SR protein with two RRM domains for RNA binding and a Cterminal RS domain for mediating protein-protein interactions during spliceosome assembly (see Fig. 1C). A total of 20 serine residues lie in the RS domain and are potential sites for phosphorylation. Mutational studies have verified that phosphorylation occurs exclusively in the RS domain (3,7,14).Although the importance of phosphorylation of SR proteins is well documented for their biological functions in splici...

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Conserved Sr Protein Kinase Functions in Nuclear Import and Its Action Is Counteracted by Arginine Methylation inSaccharomyces cerevisiae

Cited by 148 publications

References 50 publications

Interactions between two fission yeast serine/arginine-rich proteins and their modulation by phosphorylation

Interactions between two fission yeast serine/arginine-rich proteins and their modulation by phosphorylation

Control of alternative pre-mRNA splicing by Ca++ signals

Processive phosphorylation of alternative splicing factor/splicing factor 2

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