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Matthias W. Hentze - One of the best experts on this subject based on the ideXlab platform.
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A brave new world of RNA-Binding proteins
Nature Reviews Molecular Cell Biology, 2018Co-Authors: Matthias W. Hentze, Alfredo Castello, Thomas Schwarzl, Thomas PreissAbstract:Novel proteome-wide approaches, in particular RNA interactome capture, have largely expanded the repertoire of known RNA-Binding proteins (RBPs) Newly discovered RBPs generally lack canonical RNA-Binding domains (RBDs) and are functionally diverse. These unconventional RBPs are conserved from yeast to humans and respond to environmental and physiological cues A variety of protein domains endowed with RNA-Binding activity have recently been discovered, including DNA-Binding domains, protein–protein interaction interfaces, enzymatic cores and intrinsically disordered regions. These domains are prone to post-translational modifications and represent disease mutation hot spots The identification of unconventional RBPs and their unconventional RBDs suggests the existence of previously unidentified modes of RNA Binding and new biological functions for protein–RNA interactions RNA control of protein function may occur more commonly than previously anticipated Recent proteome-wide studies have uncovered hundreds of RNA-Binding proteins (RBPs) that lack conventional RNA-Binding domains. These RBPs instead use intrinsically disordered regions, protein–protein interaction interfaces and enzymatic cores to bind RNA. Interestingly, some RBPs are regulated by RNA rather than regulate RNA. RNA-Binding proteins (RBPs) are typically thought of as proteins that bind RNA through one or multiple globular RNA-Binding domains (RBDs) and change the fate or function of the bound RNAs. Several hundred such RBPs have been discovered and investigated over the years. Recent proteome-wide studies have more than doubled the number of proteins implicated in RNA Binding and uncovered hundreds of additional RBPs lacking conventional RBDs. In this Review, we discuss these new RBPs and the emerging understanding of their unexpected modes of RNA Binding, which can be mediated by intrinsically disordered regions, protein–protein interaction interfaces and enzymatic cores, among others. We also discuss the RNA targets and molecular and cellular functions of the new RBPs, as well as the possibility that some RBPs may be regulated by RNA rather than regulate RNA.
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A brave new world of RNA-Binding proteins
Nature reviews. Molecular cell biology, 2018Co-Authors: Matthias W. Hentze, Alfredo Castello, Thomas Schwarzl, Thomas PreissAbstract:RNA-Binding proteins (RBPs) are typically thought of as proteins that bind RNA through one or multiple globular RNA-Binding domains (RBDs) and change the fate or function of the bound RNAs. Several hundred such RBPs have been discovered and investigated over the years. Recent proteome-wide studies have more than doubled the number of proteins implicated in RNA Binding and uncovered hundreds of additional RBPs lacking conventional RBDs. In this Review, we discuss these new RBPs and the emerging understanding of their unexpected modes of RNA Binding, which can be mediated by intrinsically disordered regions, protein-protein interaction interfaces and enzymatic cores, among others. We also discuss the RNA targets and molecular and cellular functions of the new RBPs, as well as the possibility that some RBPs may be regulated by RNA rather than regulate RNA.
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Identification of RNA-Binding domains of RNA-Binding proteins in cultured cells on a system-wide scale with RBDmap
Nature Protocols, 2017Co-Authors: Alfredo Castello, Bernd Fischer, Christian K. Frese, Rastislav Horos, Anne-marie Alleaume, Sophia Foehr, Tomaz Curk, Jeroen Krijgsveld, Aino I Järvelin, Matthias W. HentzeAbstract:This protocol is an extension to: Nat. Protoc. 8 , 491–500 (2013); doi:10.1038/nprot.2013.020; published online 14 February 2013 RBDmap is a method for identifying, in a proteome-wide manner, the regions of RNA-Binding proteins (RBPs) engaged in native interactions with RNA. In brief, cells are irradiated with UV light to induce protein–RNA cross-links. Following stringent denaturing washes, the resulting covalently linked protein–RNA complexes are purified with oligo(dT) magnetic beads. After elution, RBPs are subjected to partial proteolysis, in which the protein regions still bound to the RNA and those released to the supeRNAtant are separated by a second oligo(dT) selection. After sample preparation and mass-spectrometric analysis, peptide intensity ratios between the RNA-bound and released fractions are used to determine the RNA-Binding regions. As a Protocol Extension, this article describes an adaptation of an existing Protocol and offers additional applications. The earlier protocol (for the RNA interactome capture method) describes how to identify the active RBPs in cultured cells, whereas this Protocol Extension also enables the identification of the RNA-Binding domains of RBPs. The experimental workflow takes 1 week plus 2 additional weeks for proteomics and data analysis. Notably, RBDmap presents numerous advantages over classic methods for determining RNA-Binding domains: it produces proteome-wide, high-resolution maps of the protein regions contacting the RNA in a physiological context and can be adapted to different biological systems and conditions. Because RBDmap relies on the isolation of polyadenylated RNA via oligo(dT), it will not provide RNA-Binding information on proteins interacting exclusively with nonpolyadenylated transcripts. Applied to HeLa cells, RBDmap uncovered 1,174 RNA-Binding sites in 529 proteins, many of which were previously unknown. Here the authors provide an extension to their earlier RNA interactome capture protocol. This Protocol Extension describes RBDmap—a method to identify the regions of RNA-Binding proteins engaged in native interactions with RNA, in a proteome-wide manner.
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Identification of RNA-Binding domains of RNA-Binding proteins in cultured cells on a system-wide scale with RBDmap
Nature protocols, 2017Co-Authors: Alfredo Castello, Bernd Fischer, Christian K. Frese, Rastislav Horos, Anne-marie Alleaume, Sophia Foehr, Tomaz Curk, Jeroen Krijgsveld, Aino I Järvelin, Matthias W. HentzeAbstract:This protocol is an extension to: Nat. Protoc. 8, 491-500 (2013); doi:10.1038/nprot.2013.020; published online 14 February 2013RBDmap is a method for identifying, in a proteome-wide manner, the regions of RNA-Binding proteins (RBPs) engaged in native interactions with RNA. In brief, cells are irradiated with UV light to induce protein-RNA cross-links. Following stringent denaturing washes, the resulting covalently linked protein-RNA complexes are purified with oligo(dT) magnetic beads. After elution, RBPs are subjected to partial proteolysis, in which the protein regions still bound to the RNA and those released to the supeRNAtant are separated by a second oligo(dT) selection. After sample preparation and mass-spectrometric analysis, peptide intensity ratios between the RNA-bound and released fractions are used to determine the RNA-Binding regions. As a Protocol Extension, this article describes an adaptation of an existing Protocol and offers additional applications. The earlier protocol (for the RNA interactome capture method) describes how to identify the active RBPs in cultured cells, whereas this Protocol Extension also enables the identification of the RNA-Binding domains of RBPs. The experimental workflow takes 1 week plus 2 additional weeks for proteomics and data analysis. Notably, RBDmap presents numerous advantages over classic methods for determining RNA-Binding domains: it produces proteome-wide, high-resolution maps of the protein regions contacting the RNA in a physiological context and can be adapted to different biological systems and conditions. Because RBDmap relies on the isolation of polyadenylated RNA via oligo(dT), it will not provide RNA-Binding information on proteins interacting exclusively with nonpolyadenylated transcripts. Applied to HeLa cells, RBDmap uncovered 1,174 RNA-Binding sites in 529 proteins, many of which were previously unknown.
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Comprehensive Identification of RNA-Binding Domains in Human Cells
Molecular cell, 2016Co-Authors: Alfredo Castello, Bernd Fischer, Christian K. Frese, Rastislav Horos, Anne-marie Alleaume, Sophia Foehr, Tomaz Curk, Jeroen Krijgsveld, Matthias W. HentzeAbstract:Mammalian cells harbor more than a thousand RNA-Binding proteins (RBPs), with half of these employing unknown modes of RNA Binding. We developed RBDmap to determine the RNA-Binding sites of native RBPs on a proteome-wide scale. We identified 1,174 Binding sites within 529 HeLa cell RBPs, discovering numerous RNA-Binding domains (RBDs). Catalytic centers or protein-protein interaction domains are in close relationship with RNA-Binding sites, invoking possible effector roles of RNA in the control of protein function. Nearly half of the RNA-Binding sites map to intrinsically disordered regions, uncovering unstructured domains as prevalent partners in protein-RNA interactions. RNA-Binding sites represent hot spots for defined posttranslational modifications such as lysine acetylation and tyrosine phosphorylation, suggesting metabolic and signal-dependent regulation of RBP function. RBDs display a high degree of evolutionary conservation and incidence of Mendelian mutations, suggestive of important functional roles. RBDmap thus yields profound insights into native protein-RNA interactions in living cells.
Alfredo Castello - One of the best experts on this subject based on the ideXlab platform.
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A brave new world of RNA-Binding proteins
Nature Reviews Molecular Cell Biology, 2018Co-Authors: Matthias W. Hentze, Alfredo Castello, Thomas Schwarzl, Thomas PreissAbstract:Novel proteome-wide approaches, in particular RNA interactome capture, have largely expanded the repertoire of known RNA-Binding proteins (RBPs) Newly discovered RBPs generally lack canonical RNA-Binding domains (RBDs) and are functionally diverse. These unconventional RBPs are conserved from yeast to humans and respond to environmental and physiological cues A variety of protein domains endowed with RNA-Binding activity have recently been discovered, including DNA-Binding domains, protein–protein interaction interfaces, enzymatic cores and intrinsically disordered regions. These domains are prone to post-translational modifications and represent disease mutation hot spots The identification of unconventional RBPs and their unconventional RBDs suggests the existence of previously unidentified modes of RNA Binding and new biological functions for protein–RNA interactions RNA control of protein function may occur more commonly than previously anticipated Recent proteome-wide studies have uncovered hundreds of RNA-Binding proteins (RBPs) that lack conventional RNA-Binding domains. These RBPs instead use intrinsically disordered regions, protein–protein interaction interfaces and enzymatic cores to bind RNA. Interestingly, some RBPs are regulated by RNA rather than regulate RNA. RNA-Binding proteins (RBPs) are typically thought of as proteins that bind RNA through one or multiple globular RNA-Binding domains (RBDs) and change the fate or function of the bound RNAs. Several hundred such RBPs have been discovered and investigated over the years. Recent proteome-wide studies have more than doubled the number of proteins implicated in RNA Binding and uncovered hundreds of additional RBPs lacking conventional RBDs. In this Review, we discuss these new RBPs and the emerging understanding of their unexpected modes of RNA Binding, which can be mediated by intrinsically disordered regions, protein–protein interaction interfaces and enzymatic cores, among others. We also discuss the RNA targets and molecular and cellular functions of the new RBPs, as well as the possibility that some RBPs may be regulated by RNA rather than regulate RNA.
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A brave new world of RNA-Binding proteins
Nature reviews. Molecular cell biology, 2018Co-Authors: Matthias W. Hentze, Alfredo Castello, Thomas Schwarzl, Thomas PreissAbstract:RNA-Binding proteins (RBPs) are typically thought of as proteins that bind RNA through one or multiple globular RNA-Binding domains (RBDs) and change the fate or function of the bound RNAs. Several hundred such RBPs have been discovered and investigated over the years. Recent proteome-wide studies have more than doubled the number of proteins implicated in RNA Binding and uncovered hundreds of additional RBPs lacking conventional RBDs. In this Review, we discuss these new RBPs and the emerging understanding of their unexpected modes of RNA Binding, which can be mediated by intrinsically disordered regions, protein-protein interaction interfaces and enzymatic cores, among others. We also discuss the RNA targets and molecular and cellular functions of the new RBPs, as well as the possibility that some RBPs may be regulated by RNA rather than regulate RNA.
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Identification of RNA-Binding domains of RNA-Binding proteins in cultured cells on a system-wide scale with RBDmap
Nature Protocols, 2017Co-Authors: Alfredo Castello, Bernd Fischer, Christian K. Frese, Rastislav Horos, Anne-marie Alleaume, Sophia Foehr, Tomaz Curk, Jeroen Krijgsveld, Aino I Järvelin, Matthias W. HentzeAbstract:This protocol is an extension to: Nat. Protoc. 8 , 491–500 (2013); doi:10.1038/nprot.2013.020; published online 14 February 2013 RBDmap is a method for identifying, in a proteome-wide manner, the regions of RNA-Binding proteins (RBPs) engaged in native interactions with RNA. In brief, cells are irradiated with UV light to induce protein–RNA cross-links. Following stringent denaturing washes, the resulting covalently linked protein–RNA complexes are purified with oligo(dT) magnetic beads. After elution, RBPs are subjected to partial proteolysis, in which the protein regions still bound to the RNA and those released to the supeRNAtant are separated by a second oligo(dT) selection. After sample preparation and mass-spectrometric analysis, peptide intensity ratios between the RNA-bound and released fractions are used to determine the RNA-Binding regions. As a Protocol Extension, this article describes an adaptation of an existing Protocol and offers additional applications. The earlier protocol (for the RNA interactome capture method) describes how to identify the active RBPs in cultured cells, whereas this Protocol Extension also enables the identification of the RNA-Binding domains of RBPs. The experimental workflow takes 1 week plus 2 additional weeks for proteomics and data analysis. Notably, RBDmap presents numerous advantages over classic methods for determining RNA-Binding domains: it produces proteome-wide, high-resolution maps of the protein regions contacting the RNA in a physiological context and can be adapted to different biological systems and conditions. Because RBDmap relies on the isolation of polyadenylated RNA via oligo(dT), it will not provide RNA-Binding information on proteins interacting exclusively with nonpolyadenylated transcripts. Applied to HeLa cells, RBDmap uncovered 1,174 RNA-Binding sites in 529 proteins, many of which were previously unknown. Here the authors provide an extension to their earlier RNA interactome capture protocol. This Protocol Extension describes RBDmap—a method to identify the regions of RNA-Binding proteins engaged in native interactions with RNA, in a proteome-wide manner.
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Identification of RNA-Binding domains of RNA-Binding proteins in cultured cells on a system-wide scale with RBDmap
Nature protocols, 2017Co-Authors: Alfredo Castello, Bernd Fischer, Christian K. Frese, Rastislav Horos, Anne-marie Alleaume, Sophia Foehr, Tomaz Curk, Jeroen Krijgsveld, Aino I Järvelin, Matthias W. HentzeAbstract:This protocol is an extension to: Nat. Protoc. 8, 491-500 (2013); doi:10.1038/nprot.2013.020; published online 14 February 2013RBDmap is a method for identifying, in a proteome-wide manner, the regions of RNA-Binding proteins (RBPs) engaged in native interactions with RNA. In brief, cells are irradiated with UV light to induce protein-RNA cross-links. Following stringent denaturing washes, the resulting covalently linked protein-RNA complexes are purified with oligo(dT) magnetic beads. After elution, RBPs are subjected to partial proteolysis, in which the protein regions still bound to the RNA and those released to the supeRNAtant are separated by a second oligo(dT) selection. After sample preparation and mass-spectrometric analysis, peptide intensity ratios between the RNA-bound and released fractions are used to determine the RNA-Binding regions. As a Protocol Extension, this article describes an adaptation of an existing Protocol and offers additional applications. The earlier protocol (for the RNA interactome capture method) describes how to identify the active RBPs in cultured cells, whereas this Protocol Extension also enables the identification of the RNA-Binding domains of RBPs. The experimental workflow takes 1 week plus 2 additional weeks for proteomics and data analysis. Notably, RBDmap presents numerous advantages over classic methods for determining RNA-Binding domains: it produces proteome-wide, high-resolution maps of the protein regions contacting the RNA in a physiological context and can be adapted to different biological systems and conditions. Because RBDmap relies on the isolation of polyadenylated RNA via oligo(dT), it will not provide RNA-Binding information on proteins interacting exclusively with nonpolyadenylated transcripts. Applied to HeLa cells, RBDmap uncovered 1,174 RNA-Binding sites in 529 proteins, many of which were previously unknown.
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Comprehensive Identification of RNA-Binding Domains in Human Cells
Molecular cell, 2016Co-Authors: Alfredo Castello, Bernd Fischer, Christian K. Frese, Rastislav Horos, Anne-marie Alleaume, Sophia Foehr, Tomaz Curk, Jeroen Krijgsveld, Matthias W. HentzeAbstract:Mammalian cells harbor more than a thousand RNA-Binding proteins (RBPs), with half of these employing unknown modes of RNA Binding. We developed RBDmap to determine the RNA-Binding sites of native RBPs on a proteome-wide scale. We identified 1,174 Binding sites within 529 HeLa cell RBPs, discovering numerous RNA-Binding domains (RBDs). Catalytic centers or protein-protein interaction domains are in close relationship with RNA-Binding sites, invoking possible effector roles of RNA in the control of protein function. Nearly half of the RNA-Binding sites map to intrinsically disordered regions, uncovering unstructured domains as prevalent partners in protein-RNA interactions. RNA-Binding sites represent hot spots for defined posttranslational modifications such as lysine acetylation and tyrosine phosphorylation, suggesting metabolic and signal-dependent regulation of RBP function. RBDs display a high degree of evolutionary conservation and incidence of Mendelian mutations, suggestive of important functional roles. RBDmap thus yields profound insights into native protein-RNA interactions in living cells.
André P. Gerber - One of the best experts on this subject based on the ideXlab platform.
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Unconventional RNA‐Binding proteins: an uncharted zone in RNA biology
FEBS Letters, 2018Co-Authors: Waleed S. Albihlal, André P. GerberAbstract:RNA-Binding proteins play essential roles in the post-transcriptional regulation of gene expression. While hundreds of RNA-Binding proteins can be predicted computationally, the recent introduction of proteome-wide approaches has dramatically expanded the repertoire of proteins interacting with RNA. Besides canonical RNA-Binding proteins that contain characteristic RNA-Binding domains, many proteins that lack such domains but have other well-characterised cellular functions were identified; including metabolic enzymes, heat shock proteins, kinases, as well as transcription factors and chromatin-associated proteins. In the context of these recently published RNA-protein interactome datasets obtained from yeast, nematodes, flies, plants and mammalian cells, we discuss examples for seemingly evolutionary conserved “unconventional” RNA-Binding proteins that act in central carbon metabolism, stress response or regulation of transcription.
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Unconventional RNA‐Binding proteins: an uncharted zone in RNA biology
FEBS letters, 2018Co-Authors: Waleed S. Albihlal, André P. GerberAbstract:The RNA-Binding proteins play essential roles in the post-transcriptional regulation of gene expression. While hundreds of RNA-Binding proteins can be predicted computationally, the recent introduction of proteome-wide approaches has dramatically expanded the repertoire of proteins interacting with RNA. Besides canonical RNA-Binding proteins that contain characteristic RNA-Binding domains, many proteins that lack such domains but have other well-characterized cellular functions were identified; including metabolic enzymes, heat shock proteins, kinases, as well as transcription factors and chromatin-associated proteins. In the context of these recently published RNA-protein interactome datasets obtained from yeast, nematodes, flies, plants and mammalian cells, we discuss examples for seemingly evolutionary conserved 'unconventional' RNA-Binding proteins that act in central carbon metabolism, stress response or regulation of transcription.
Bernd Fischer - One of the best experts on this subject based on the ideXlab platform.
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Identification of RNA-Binding domains of RNA-Binding proteins in cultured cells on a system-wide scale with RBDmap
Nature Protocols, 2017Co-Authors: Alfredo Castello, Bernd Fischer, Christian K. Frese, Rastislav Horos, Anne-marie Alleaume, Sophia Foehr, Tomaz Curk, Jeroen Krijgsveld, Aino I Järvelin, Matthias W. HentzeAbstract:This protocol is an extension to: Nat. Protoc. 8 , 491–500 (2013); doi:10.1038/nprot.2013.020; published online 14 February 2013 RBDmap is a method for identifying, in a proteome-wide manner, the regions of RNA-Binding proteins (RBPs) engaged in native interactions with RNA. In brief, cells are irradiated with UV light to induce protein–RNA cross-links. Following stringent denaturing washes, the resulting covalently linked protein–RNA complexes are purified with oligo(dT) magnetic beads. After elution, RBPs are subjected to partial proteolysis, in which the protein regions still bound to the RNA and those released to the supeRNAtant are separated by a second oligo(dT) selection. After sample preparation and mass-spectrometric analysis, peptide intensity ratios between the RNA-bound and released fractions are used to determine the RNA-Binding regions. As a Protocol Extension, this article describes an adaptation of an existing Protocol and offers additional applications. The earlier protocol (for the RNA interactome capture method) describes how to identify the active RBPs in cultured cells, whereas this Protocol Extension also enables the identification of the RNA-Binding domains of RBPs. The experimental workflow takes 1 week plus 2 additional weeks for proteomics and data analysis. Notably, RBDmap presents numerous advantages over classic methods for determining RNA-Binding domains: it produces proteome-wide, high-resolution maps of the protein regions contacting the RNA in a physiological context and can be adapted to different biological systems and conditions. Because RBDmap relies on the isolation of polyadenylated RNA via oligo(dT), it will not provide RNA-Binding information on proteins interacting exclusively with nonpolyadenylated transcripts. Applied to HeLa cells, RBDmap uncovered 1,174 RNA-Binding sites in 529 proteins, many of which were previously unknown. Here the authors provide an extension to their earlier RNA interactome capture protocol. This Protocol Extension describes RBDmap—a method to identify the regions of RNA-Binding proteins engaged in native interactions with RNA, in a proteome-wide manner.
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Identification of RNA-Binding domains of RNA-Binding proteins in cultured cells on a system-wide scale with RBDmap
Nature protocols, 2017Co-Authors: Alfredo Castello, Bernd Fischer, Christian K. Frese, Rastislav Horos, Anne-marie Alleaume, Sophia Foehr, Tomaz Curk, Jeroen Krijgsveld, Aino I Järvelin, Matthias W. HentzeAbstract:This protocol is an extension to: Nat. Protoc. 8, 491-500 (2013); doi:10.1038/nprot.2013.020; published online 14 February 2013RBDmap is a method for identifying, in a proteome-wide manner, the regions of RNA-Binding proteins (RBPs) engaged in native interactions with RNA. In brief, cells are irradiated with UV light to induce protein-RNA cross-links. Following stringent denaturing washes, the resulting covalently linked protein-RNA complexes are purified with oligo(dT) magnetic beads. After elution, RBPs are subjected to partial proteolysis, in which the protein regions still bound to the RNA and those released to the supeRNAtant are separated by a second oligo(dT) selection. After sample preparation and mass-spectrometric analysis, peptide intensity ratios between the RNA-bound and released fractions are used to determine the RNA-Binding regions. As a Protocol Extension, this article describes an adaptation of an existing Protocol and offers additional applications. The earlier protocol (for the RNA interactome capture method) describes how to identify the active RBPs in cultured cells, whereas this Protocol Extension also enables the identification of the RNA-Binding domains of RBPs. The experimental workflow takes 1 week plus 2 additional weeks for proteomics and data analysis. Notably, RBDmap presents numerous advantages over classic methods for determining RNA-Binding domains: it produces proteome-wide, high-resolution maps of the protein regions contacting the RNA in a physiological context and can be adapted to different biological systems and conditions. Because RBDmap relies on the isolation of polyadenylated RNA via oligo(dT), it will not provide RNA-Binding information on proteins interacting exclusively with nonpolyadenylated transcripts. Applied to HeLa cells, RBDmap uncovered 1,174 RNA-Binding sites in 529 proteins, many of which were previously unknown.
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Comprehensive Identification of RNA-Binding Domains in Human Cells
Molecular cell, 2016Co-Authors: Alfredo Castello, Bernd Fischer, Christian K. Frese, Rastislav Horos, Anne-marie Alleaume, Sophia Foehr, Tomaz Curk, Jeroen Krijgsveld, Matthias W. HentzeAbstract:Mammalian cells harbor more than a thousand RNA-Binding proteins (RBPs), with half of these employing unknown modes of RNA Binding. We developed RBDmap to determine the RNA-Binding sites of native RBPs on a proteome-wide scale. We identified 1,174 Binding sites within 529 HeLa cell RBPs, discovering numerous RNA-Binding domains (RBDs). Catalytic centers or protein-protein interaction domains are in close relationship with RNA-Binding sites, invoking possible effector roles of RNA in the control of protein function. Nearly half of the RNA-Binding sites map to intrinsically disordered regions, uncovering unstructured domains as prevalent partners in protein-RNA interactions. RNA-Binding sites represent hot spots for defined posttranslational modifications such as lysine acetylation and tyrosine phosphorylation, suggesting metabolic and signal-dependent regulation of RBP function. RBDs display a high degree of evolutionary conservation and incidence of Mendelian mutations, suggestive of important functional roles. RBDmap thus yields profound insights into native protein-RNA interactions in living cells.
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RNA-Binding proteins in Mendelian disease
Trends in genetics : TIG, 2013Co-Authors: Alfredo Castello, Bernd Fischer, Matthias W. Hentze, Thomas PreissAbstract:RNA-Binding proteins (RBPs) control all aspects of RNA fate, and defects in their function underlie a broad spectrum of human pathologies. We focus here on two recent studies that uncovered the in vivo mRNA interactomes of human cells, jointly implicating over 1100 proteins in RNA Binding. Surprisingly, over 350 of these RBPs had no prior RNA Binding-related annotation or domain homology. The datasets also contain many proteins that, when mutated, cause Mendelian diseases, prominently neurological, sensory, and muscular disorders and cancers. Disease mutations in these proteins occur throughout their domain architectures and many are found in non-classical RNA-Binding domains and in disordered regions. In some cases, mutations might cause disease through perturbing previously unknown RNA-related protein functions. These studies have thus expanded our knowledge of RBPs and their role in genetic diseases. We also expect that mRNA interactome capture approaches will aid further exploration of RNA systems biology in varied physiological and pathophysiological settings.
Waleed S. Albihlal - One of the best experts on this subject based on the ideXlab platform.
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Unconventional RNA‐Binding proteins: an uncharted zone in RNA biology
FEBS Letters, 2018Co-Authors: Waleed S. Albihlal, André P. GerberAbstract:RNA-Binding proteins play essential roles in the post-transcriptional regulation of gene expression. While hundreds of RNA-Binding proteins can be predicted computationally, the recent introduction of proteome-wide approaches has dramatically expanded the repertoire of proteins interacting with RNA. Besides canonical RNA-Binding proteins that contain characteristic RNA-Binding domains, many proteins that lack such domains but have other well-characterised cellular functions were identified; including metabolic enzymes, heat shock proteins, kinases, as well as transcription factors and chromatin-associated proteins. In the context of these recently published RNA-protein interactome datasets obtained from yeast, nematodes, flies, plants and mammalian cells, we discuss examples for seemingly evolutionary conserved “unconventional” RNA-Binding proteins that act in central carbon metabolism, stress response or regulation of transcription.
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Unconventional RNA‐Binding proteins: an uncharted zone in RNA biology
FEBS letters, 2018Co-Authors: Waleed S. Albihlal, André P. GerberAbstract:The RNA-Binding proteins play essential roles in the post-transcriptional regulation of gene expression. While hundreds of RNA-Binding proteins can be predicted computationally, the recent introduction of proteome-wide approaches has dramatically expanded the repertoire of proteins interacting with RNA. Besides canonical RNA-Binding proteins that contain characteristic RNA-Binding domains, many proteins that lack such domains but have other well-characterized cellular functions were identified; including metabolic enzymes, heat shock proteins, kinases, as well as transcription factors and chromatin-associated proteins. In the context of these recently published RNA-protein interactome datasets obtained from yeast, nematodes, flies, plants and mammalian cells, we discuss examples for seemingly evolutionary conserved 'unconventional' RNA-Binding proteins that act in central carbon metabolism, stress response or regulation of transcription.
