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  1. Article: Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors.

    Kretova, Miroslava / Selicky, Tomas / Cipakova, Ingrid / Cipak, Lubos

    Life (Basel, Switzerland)

    2023  Volume 13, Issue 3

    Abstract: Pre-mRNA splicing is a process used by eukaryotic cells to generate messenger RNAs that can be translated into proteins. During splicing, the non-coding regions of the RNAs (introns) are removed from pre-mRNAs and the coding regions (exons) are joined ... ...

    Abstract Pre-mRNA splicing is a process used by eukaryotic cells to generate messenger RNAs that can be translated into proteins. During splicing, the non-coding regions of the RNAs (introns) are removed from pre-mRNAs and the coding regions (exons) are joined together, resulting in mature mRNAs. The particular steps of splicing are executed by the multimegadalton complex called a spliceosome. This complex is composed of small nuclear ribonucleoproteins, various splicing factors, and other regulatory and auxiliary proteins. In recent years, various post-translational modifications of splicing factors have been shown to contribute significantly to regulation of processes involved in pre-mRNA splicing. In this review, we provide an overview of the most important post-translational modifications of splicing factors that are indispensable for their normal function during pre-mRNA splicing (i.e., phosphorylation, acetylation, methylation, ubiquitination and sumoylation). Moreover, we also discuss how the defects in regulation of splicing factors are related to the development of cancer.
    Language English
    Publishing date 2023-02-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life13030604
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Dysfunction of Gpl1-Gih35-Wdr83 Complex in

    Cipakova, Ingrid / Jurcik, Matus / Selicky, Tomas / Lalakova, Laura Olivia / Jakubikova, Jana / Cipak, Lubos

    International journal of molecular sciences

    2024  Volume 25, Issue 8

    Abstract: Pre-mRNA splicing plays a key role in the regulation of gene expression. Recent discoveries suggest that defects in pre-mRNA splicing, resulting from the dysfunction of certain splicing factors, can impact the expression of genes crucial for genome ... ...

    Abstract Pre-mRNA splicing plays a key role in the regulation of gene expression. Recent discoveries suggest that defects in pre-mRNA splicing, resulting from the dysfunction of certain splicing factors, can impact the expression of genes crucial for genome surveillance mechanisms, including those involved in cellular response to DNA damage. In this study, we analyzed how cells with a non-functional spliceosome-associated Gpl1-Gih35-Wdr83 complex respond to DNA damage. Additionally, we investigated the role of this complex in regulating the splicing of factors involved in DNA damage repair. Our findings reveal that the deletion of any component within the Gpl1-Gih35-Wdr83 complex leads to a significant accumulation of unspliced pre-mRNAs of DNA repair factors. Consequently, mutant cells lacking this complex exhibit increased sensitivity to DNA-damaging agents. These results highlight the importance of the Gpl1-Gih35-Wdr83 complex in regulating the expression of DNA repair factors, thereby protecting the stability of the genome following DNA damage.
    MeSH term(s) DNA Damage ; DNA Repair ; RNA Splicing ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism ; Spliceosomes/metabolism ; Spliceosomes/genetics ; RNA Splicing Factors/metabolism ; RNA Splicing Factors/genetics ; Gene Expression Regulation, Fungal ; RNA Precursors/genetics ; RNA Precursors/metabolism
    Chemical Substances Schizosaccharomyces pombe Proteins ; RNA Splicing Factors ; RNA Precursors
    Language English
    Publishing date 2024-04-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25084192
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Interplay of Cohesin and RNA Processing Factors: The Impact of Their Alterations on Genome Stability.

    Osadska, Michaela / Selicky, Tomas / Kretova, Miroslava / Jurcik, Jan / Sivakova, Barbara / Cipakova, Ingrid / Cipak, Lubos

    International journal of molecular sciences

    2022  Volume 23, Issue 7

    Abstract: Cohesin, a multi-subunit protein complex, plays important roles in sister chromatid cohesion, DNA replication, chromatin organization, gene expression, transcription regulation, and the recombination or repair of DNA damage. Recently, several studies ... ...

    Abstract Cohesin, a multi-subunit protein complex, plays important roles in sister chromatid cohesion, DNA replication, chromatin organization, gene expression, transcription regulation, and the recombination or repair of DNA damage. Recently, several studies suggested that the functions of cohesin rely not only on cohesin-related protein-protein interactions, their post-translational modifications or specific DNA modifications, but that some RNA processing factors also play an important role in the regulation of cohesin functions. Therefore, the mutations and changes in the expression of cohesin subunits or alterations in the interactions between cohesin and RNA processing factors have been shown to have an impact on cohesion, the fidelity of chromosome segregation and, ultimately, on genome stability. In this review, we provide an overview of the cohesin complex and its role in chromosome segregation, highlight the causes and consequences of mutations and changes in the expression of cohesin subunits, and discuss the RNA processing factors that participate in the regulation of the processes involved in chromosome segregation. Overall, an understanding of the molecular determinants of the interplay between cohesin and RNA processing factors might help us to better understand the molecular mechanisms ensuring the integrity of the genome.
    MeSH term(s) Cell Cycle Proteins/metabolism ; Chromatids/metabolism ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosome Segregation ; Genomic Instability ; Humans ; RNA Processing, Post-Transcriptional ; Cohesins
    Chemical Substances Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone
    Language English
    Publishing date 2022-04-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23073939
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Label-Free Quantitative Phosphoproteomics of the Fission Yeast

    Sivakova, Barbara / Jurcik, Jan / Lukacova, Veronika / Selicky, Tomas / Cipakova, Ingrid / Barath, Peter / Cipak, Lubos

    International journal of molecular sciences

    2021  Volume 22, Issue 4

    Abstract: The phosphorylation of proteins modulates various functions of proteins and plays an important role in the regulation of cell signaling. In recent years, label-free quantitative (LFQ) phosphoproteomics has become a powerful tool to analyze the ... ...

    Abstract The phosphorylation of proteins modulates various functions of proteins and plays an important role in the regulation of cell signaling. In recent years, label-free quantitative (LFQ) phosphoproteomics has become a powerful tool to analyze the phosphorylation of proteins within complex samples. Despite the great progress, the studies of protein phosphorylation are still limited in throughput, robustness, and reproducibility, hampering analyses that involve multiple perturbations, such as those needed to follow the dynamics of phosphoproteomes. To address these challenges, we introduce here the LFQ phosphoproteomics workflow that is based on Fe-IMAC phosphopeptide enrichment followed by strong anion exchange (SAX) and porous graphitic carbon (PGC) fractionation strategies. We applied this workflow to analyze the whole-cell phosphoproteome of the fission yeast
    MeSH term(s) Anion Exchange Resins/chemistry ; Carbon/chemistry ; Chemical Fractionation/methods ; Chromatography, Ion Exchange/methods ; Graphite/chemistry ; Phosphoproteins/analysis ; Phosphoproteins/chemistry ; Porosity ; Proteomics/methods ; Reproducibility of Results ; Schizosaccharomyces ; Schizosaccharomyces pombe Proteins/analysis ; Schizosaccharomyces pombe Proteins/chemistry
    Chemical Substances Anion Exchange Resins ; Phosphoproteins ; Schizosaccharomyces pombe Proteins ; Carbon (7440-44-0) ; Graphite (7782-42-5)
    Language English
    Publishing date 2021-02-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22041747
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Tandem affinity purification protocol for isolation of protein complexes from

    Cipak, Lubos / Selicky, Tomas / Jurcik, Jan / Cipakova, Ingrid / Osadska, Michaela / Lukacova, Veronika / Barath, Peter / Gregan, Juraj

    STAR protocols

    2022  Volume 3, Issue 1, Page(s) 101137

    Abstract: Many cellular processes require the activities of complex molecular machines composed of several protein subunits. Insights into these systems can be gained by isolation of protein complexes followed ... ...

    Abstract Many cellular processes require the activities of complex molecular machines composed of several protein subunits. Insights into these systems can be gained by isolation of protein complexes followed by
    MeSH term(s) Mass Spectrometry ; Proteins/metabolism ; Schizosaccharomyces/genetics ; Tandem Affinity Purification
    Chemical Substances Proteins
    Language English
    Publishing date 2022-01-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2022.101137
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Phosphoproteomics Meets Chemical Genetics: Approaches for Global Mapping and Deciphering the Phosphoproteome.

    Jurcik, Jan / Sivakova, Barbara / Cipakova, Ingrid / Selicky, Tomas / Stupenova, Erika / Jurcik, Matus / Osadska, Michaela / Barath, Peter / Cipak, Lubos

    International journal of molecular sciences

    2020  Volume 21, Issue 20

    Abstract: Protein kinases are important enzymes involved in the regulation of various cellular processes. To function properly, each protein kinase phosphorylates only a limited number of proteins among the thousands present in the cell. This provides a rapid and ... ...

    Abstract Protein kinases are important enzymes involved in the regulation of various cellular processes. To function properly, each protein kinase phosphorylates only a limited number of proteins among the thousands present in the cell. This provides a rapid and dynamic regulatory mechanism that controls biological functions of the proteins. Despite the importance of protein kinases, most of their substrates remain unknown. Recently, the advances in the fields of protein engineering, chemical genetics, and mass spectrometry have boosted studies on identification of bona fide substrates of protein kinases. Among the various methods in protein kinase specific substrate identification, genetically engineered protein kinases and quantitative phosphoproteomics have become promising tools. Herein, we review the current advances in the field of chemical genetics in analog-sensitive protein kinase mutants and highlight selected strategies for identifying protein kinase substrates and studying the dynamic nature of protein phosphorylation.
    MeSH term(s) Animals ; Humans ; Mass Spectrometry/methods ; Phosphoproteins/chemistry ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Protein Interaction Mapping/methods ; Protein Kinases/chemistry ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Proteome/chemistry ; Proteome/genetics ; Proteome/metabolism ; Proteomics/methods
    Chemical Substances Phosphoproteins ; Proteome ; Protein Kinases (EC 2.7.-)
    Language English
    Publishing date 2020-10-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21207637
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Defining the Functional Interactome of Spliceosome-Associated G-Patch Protein Gpl1 in the Fission Yeast

    Selicky, Tomas / Jurcik, Matus / Mikolaskova, Barbora / Pitelova, Alexandra / Mayerova, Nina / Kretova, Miroslava / Osadska, Michaela / Jurcik, Jan / Holic, Roman / Kohutova, Lenka / Bellova, Jana / Benko, Zsigmond / Gregan, Juraj / Bagelova Polakova, Silvia / Barath, Peter / Cipak, Lubos / Cipakova, Ingrid

    International journal of molecular sciences

    2022  Volume 23, Issue 21

    Abstract: Pre-mRNA splicing plays a fundamental role in securing protein diversity by generating multiple transcript isoforms from a single gene. Recently, it has been shown that specific G-patch domain-containing proteins are critical cofactors involved in the ... ...

    Abstract Pre-mRNA splicing plays a fundamental role in securing protein diversity by generating multiple transcript isoforms from a single gene. Recently, it has been shown that specific G-patch domain-containing proteins are critical cofactors involved in the regulation of splicing processes. In this study, using the knock-out strategy, affinity purification and the yeast-two-hybrid assay, we demonstrated that the spliceosome-associated G-patch protein Gpl1 of the fission yeast
    MeSH term(s) Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Spliceosomes/genetics ; Spliceosomes/metabolism ; RNA Precursors/genetics ; RNA Splicing ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism
    Chemical Substances RNA Precursors ; Schizosaccharomyces pombe Proteins
    Language English
    Publishing date 2022-10-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms232112800
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Identification of Nrl1 Domains Responsible for Interactions with RNA-Processing Factors and Regulation of Nrl1 Function by Phosphorylation.

    Mikolaskova, Barbora / Jurcik, Matus / Cipakova, Ingrid / Selicky, Tomas / Jurcik, Jan / Polakova, Silvia Bagelova / Stupenova, Erika / Dudas, Andrej / Sivakova, Barbara / Bellova, Jana / Barath, Peter / Aronica, Lucia / Gregan, Juraj / Cipak, Lubos

    International journal of molecular sciences

    2021  Volume 22, Issue 13

    Abstract: Pre-mRNA splicing is a key process in the regulation of gene expression. In the fission ... ...

    Abstract Pre-mRNA splicing is a key process in the regulation of gene expression. In the fission yeast
    MeSH term(s) Casein Kinase II/metabolism ; Phosphorylation ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Interaction Mapping ; RNA Processing, Post-Transcriptional ; RNA Splicing ; RNA-Binding Proteins/metabolism ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/chemistry ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism ; Schizosaccharomyces pombe Proteins/physiology ; Spliceosomes/metabolism ; Two-Hybrid System Techniques
    Chemical Substances Nrl1 protein, S pombe ; RNA-Binding Proteins ; Schizosaccharomyces pombe Proteins ; Casein Kinase II (EC 2.7.11.1)
    Language English
    Publishing date 2021-06-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22137011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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