The Experts below are selected from a list of 17118 Experts worldwide ranked by ideXlab platform
Patrick Linder - One of the best experts on this subject based on the ideXlab platform.
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Happy Birthday: 30 Years of RNA Helicases.
Methods in molecular biology (Clifton N.J.), 2020Co-Authors: Martina Valentini, Patrick LinderAbstract:RNA Helicases are ubiquitous, highly conserved RNA-binding enzymes that use the energy derived from the hydrolysis of nucleoside triphosphate to modify the structure of RNA molecules and/or the functionality of ribonucleoprotein complexes. Ultimately, the action of RNA Helicases results in changes in gene expression that allow the cell to perform crucial functions. In this chapter, we review established and emerging concepts for DEAD-box and DExH-box RNA Helicases. We mention examples from both eukaryotic and prokaryotic systems, in order to highlight common themes and specific actions.
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RNA Helicases in RNA decay
Biochemical Society transactions, 2018Co-Authors: Vanessa Khemici, Patrick LinderAbstract:RNA molecules have the tendency to fold into complex structures or to associate with complementary RNAs that exoribonucleases have difficulties processing or degrading. Therefore, degradosomes in bacteria and organelles as well as exosomes in eukaryotes have teamed-up with RNA Helicases. Whereas bacterial degradosomes are associated with RNA Helicases from the DEAD-box family, the exosomes and mitochondrial degradosome use the help of Ski2-like and Suv3 RNA Helicases.
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bacterial versatility requires dead box RNA Helicases
Fems Microbiology Reviews, 2015Co-Authors: Peter Redder, Vanessa Khemici, Stephane Hausmann, Haleh Yasrebi, Patrick LinderAbstract:RNA Helicases of the DEAD-box and DEAH-box families are important players in many processes involving RNA molecules. These proteins can modify RNA secondary structures or intermolecular RNA interactions and modulate RNA-protein complexes. In bacteria, they are known to be involved in ribosome biogenesis, RNA turnover and translation initiation. They thereby play an important role in the adaptation of bacteria to changing environments and to respond to stress conditions.
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looking back on the birth of dead box RNA Helicases
Biochimica et Biophysica Acta, 2013Co-Authors: Patrick Linder, Frances V FullerpaceAbstract:DEAD-box proteins represent the largest family of RNA Helicases, present in all three kingdoms of life. They are involved in a variety of processes involving RNA metabolism and in some instances also in processes that use guide RNAs. Since their first descriptions in the late 1980s, the perception of their molecular activities has dramatically changed. At the time when only eight proteins with 9 conserved motifs constituted the DEAD-box protein family, it was the biochemical characterization of mammalian eIF4A that first suggested a local unwinding activity. This was confirmed in vitro using partially double stranded RNA substrates with the unexpected result of a bidirectional unwinding activity. A real change of paradigm from the classical helicase activity to localized RNA unwinding occurred with the publication of the vasa•RNA structure with a bend in the RNA substrate and the insightful work from several laboratories demonstrating local unwinding without translocation. Finally, elegant work on the exon-junction complex revealed how DEAD-box proteins can bind to RNA to serve as clamps to function as nucleation centers to form RNP complexes. This article is part of a Special Issue entitled: The Biology of RNA Helicases - Modulation for life.
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Plant RNA Helicases: linking aberrant and silencing RNA
Trends in Plant Science, 2009Co-Authors: Patrick Linder, George W. OwttrimAbstract:RNA Helicases are ATPases that are capable of rearranging RNA and ribonucleoprotein (RNP) structure, and they can potentially function in any aspect of RNA metabolism. The RNA helicase gene family of plant genomes is larger and more diverse than genome families observed in other systems and provides an ideal model for investigation of the physiological importance of RNA secondary structure rearrangement in plant development. Numerous plant RNA Helicases are associated with a variety of physiological functions, but this review will focus on the thirteen RNA Helicases associated with the metabolism of aberrant and silencing RNAs. The results emphasize the crucial role RNA helicase activity has in the regulation of mRNA quality control and gene expression in plant development.
Susan J. Baserga - One of the best experts on this subject based on the ideXlab platform.
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In Vivo Approaches to Dissecting the Function of RNA Helicases in Eukaryotic Ribosome Assembly
Methods in Enzymology, 2012Co-Authors: David C. Rawling, Susan J. BasergaAbstract:In eukaryotes, ribosome biogenesis involves the nucleolar transcription and processing of pre-ribosomal RNA molecules (pre-rRNA) in a complex pathway requiring the participation of myriad protein and ribonucleoprotein factors. Through efforts aimed at categorizing and characterizing these factors, at least 20 RNA Helicases have been shown to interact with or participate in the activities of the major ribosome biogenesis complexes. Unfortunately, little is known about the enzymatic properties of most of these Helicases, and less is known about their roles in ribosome biogenesis and pre-rRNA maturation. This chapter presents approaches for characterizing RNA Helicases involved in ribosome biogenesis. Included are methods for depletion of specific protein targets, with standard protocols for assaying the typical ribosome biogenesis defects that may result. Procedures and rationales for mutagenic studies of target proteins are discussed, as well as several approaches for identifying protein–protein interactions in order to determine functional context and potential cofactors of RNA Helicases.
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The Long Unwinding Road of RNA Helicases
Molecular cell, 2007Co-Authors: Franziska Bleichert, Susan J. BasergaAbstract:RNA Helicases comprise a large family of enzymes that are thought to utilize the energy of NTP binding and hydrolysis to remodel RNA or RNA-protein complexes, resulting in RNA duplex strand separation, displacement of proteins from RNA molecules, or both. These functions of RNA Helicases are required for all aspects of cellular RNA metabolism, from bacteria to humans. We provide a brief overview of the functions of RNA Helicases and highlight some of the recent key advances that have contributed to our current understanding of their biological function and mechanism of action.
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comprehensive mutational analysis of yeast dexd h box RNA Helicases involved in large ribosomal subunit biogenesis
Molecular and Cellular Biology, 2006Co-Authors: Kara A Bernstein, Sander Granneman, Alicia V Lee, Swarnameenakshi Manickam, Susan J. BasergaAbstract:DEXD/H box putative RNA Helicases are required for pre-rRNA processing in Saccharomyces cerevisiae, although their exact roles and substrates are unknown. To characterize the significance of the conserved motifs for helicase function, a series of five mutations were created in each of the eight essential RNA Helicases (Has1, Dbp6, Dbp10, Mak5, Mtr4, Drs1, Spb4, and Dbp9) involved in 60S ribosomal subunit biogenesis. Each mutant helicase was screened for the ability to confer dominant negative growth defects and for functional complementation. Different mutations showed different degrees of growth inhibition among the Helicases, suggesting that the conserved regions do not function identically in vivo. Mutations in motif I and motif II (the DEXD/H box) often conferred dominant negative growth defects, indicating that these mutations do not interfere with substrate binding. In addition, mutations in the putative unwinding domains (motif III) demonstrated that conserved amino acids are often not essential for function. Northern analysis of steady-state RNA from strains expressing mutant Helicases showed that the dominant negative mutations also altered pre-rRNA processing. Coimmunoprecipitation experiments indicated that some RNA Helicases associated with each other. In addition, we found that yeasts disrupted in expression of the two nonessential RNA Helicases, Dbp3 and Dbp7, grew worse than when either one alone was disrupted.
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comprehensive mutational analysis of yeast dexd h box RNA Helicases required for small ribosomal subunit synthesis
Molecular and Cellular Biology, 2006Co-Authors: Sander Granneman, Kara A Bernstein, Franziska Bleichert, Susan J. BasergaAbstract:The 17 putative RNA Helicases required for pre-rRNA processing are predicted to play a crucial role in ribosome biogenesis by driving structural rearrangements within preribosomes. To better understand the function of these proteins, we have generated a battery of mutations in five putative RNA Helicases involved in 18S rRNA synthesis and analyzed their effects on cell growth and pre-rRNA processing. Our results define functionally important residues within conserved motifs and demonstrate that lethal mutations in predicted ATP binding-hydrolysis motifs often confer a dominant negative phenotype in vivo when overexpressed in a wild-type background. We show that dominant negative mutants delay processing of the 35S pre-rRNA and cause accumulation of pre-rRNA species that normally have low steady-state levels. Our combined results establish that not all conserved domains function identically in each protein, suggesting that the RNA Helicases may have distinct biochemical properties and diverse roles in ribosome biogenesis.
Kathleen Boris-lawrie - One of the best experts on this subject based on the ideXlab platform.
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Cellular RNA Helicases and HIV-1: insights from genome-wide, proteomic, and molecular studies.
Virus research, 2012Co-Authors: Chia-yen Chen, Amit Sharma, Kathleen Boris-lawrie, Xiang Liu, Kuan-teh JeangAbstract:RNA Helicases are ubiquitous in plants and animals and function in many cellular processes. Retroviruses, such as human immunodeficiency virus (HIV-1), encode no RNA Helicases in their genomes and utilize host cellular RNA Helicases at various stages of their life cycle. Here, we briefly summarize the roles RNA Helicases play in HIV-1 replication that have been identified recently, in part, through genome-wide screenings, proteomics, and molecular studies. Some of these Helicases augment virus propagation while others apparently participate in antiviral defenses against viral replication.
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Determination of host RNA Helicases activity in viral replication.
Methods in Enzymology, 2012Co-Authors: Amit Sharma, Kathleen Boris-lawrieAbstract:RNA Helicases are encoded by all eukaryotic and prokaryotic cells and a minority of viruses. Activity of RNA Helicases is necessary for all steps in the expression of cells and viruses and the host innate response to virus infection. Their vast functional repertoire is attributable to the core ATP-dependent helicase domain in conjunction with flanking domains that are interchangeable and engage viral and cellular cofactors. Here, we address the important issue of host RNA Helicases that are necessary for replication of a virus. This chapter covers approaches to identification and characterization of candidate Helicases and methods to define the biochemical and biophysical parameters of specificity and functional activity of the enzymes. We discuss the context of cellular RNA helicase activity and virion-associated RNA Helicases. The methodology and choice of controls fosters the assessment of the virologic scope of RNA Helicases across divergent cell lineages and viral replication cycles.
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RNA Helicases: Emerging roles in viral replication and the host innate response
RNA biology, 2010Co-Authors: Arnaz Ranji, Kathleen Boris-lawrieAbstract:RNA Helicases serve multiple roles at the virus-host interface. In some situations, RNA Helicases are essential host factors to promote viral replication; however, in other cases they serve as a cellular sensor to trigger the antiviral state in response to viral infection. All family members share the conserved ATP-dependent catalytic core linked to different substrate recognition and protein-protein interaction domains. These flanking domains can be shuffled between different Helicases to achieve functional diversity. This review summarizes recent studies, which have revealed two types of activity by RNA Helicases. First, RNA Helicases are catalysts of progressive RNA-protein rearrangements that begin at gene transcription and culminate in mRNA translation. Second, RNA Helicases can act as a scaffold for alteRNAtive protein-protein interactions that can defeat the antiviral state. The mounting fundamental understanding of RNA Helicases is being used to develop selective and efficacious drugs against huma...
Sun Hur - One of the best experts on this subject based on the ideXlab platform.
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Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA Helicases and TRIM ubiquitin ligases.
Molecular cell, 2020Co-Authors: Kazuki Kato, Sadeem Ahmad, Zixiang Zhu, Janet M Young, Sehoon Park, Harmit S Malik, Sun HurAbstract:RNA Helicases and E3 ubiquitin ligases mediate many critical functions in cells, but their actions have largely been studied in distinct biological contexts. Here, we uncover evolutionarily conserved rules of engagement between RNA Helicases and tripartite motif (TRIM) E3 ligases that lead to their functional coordination in vertebrate innate immunity. Using cryoelectron microscopy and biochemistry, we show that RIG-I-like receptors (RLRs), viral RNA receptors with helicase domains, interact with their cognate TRIM/TRIM-like E3 ligases through similar epitopes in the helicase domains. Their interactions are avidity driven, restricting the actions of TRIM/TRIM-like proteins and consequent immune activation to RLR multimers. Mass spectrometry and phylogeny-guided biochemical analyses further reveal that similar rules of engagement may apply to diverse RNA Helicases and TRIM/TRIM-like proteins. Our analyses suggest not only conserved substrates for TRIM proteins but also, unexpectedly, deep evolutionary connections between TRIM proteins and RNA Helicases, linking ubiquitin and RNA biology throughout animal evolution.
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structural analysis of rig i like receptors reveals ancient rules of engagement between diverse RNA Helicases and trim ubiquitin ligases
bioRxiv, 2020Co-Authors: Kazuki Kato, Sadeem Ahmad, Zixiang Zhu, Janet M Young, Sehoon Park, Harmit S Malik, Sun HurAbstract:RNA Helicases and ubiquitin E3 ligases mediate many critical functions within cells, but their actions have been studied largely in distinct biological contexts. Here, we uncover evolutionarily conserved rules of engagement between RNA Helicases and tripartite motif (TRIM) E3 ligases that lead to their functional coordination in vertebrate innate immunity. Using cryo-electron microscopy and biochemistry, we show that RIG-I-like receptors (RLRs), viral RNA receptors with helicase domains, interact with their cognate TRIM/TRIM-like E3 ligases through similar epitopes in the helicase domains. Their interactions are avidity-driven, restricting the actions of TRIM/TRIM-like proteins and consequent immune activation to RLR multimers. Mass-spectrometry and phylogeny-guided biochemical analyses further reveal that similar rules of engagement apply to diverse RNA Helicases and TRIM/TRIM-like proteins. Our analyses thus reveal not only conserved substrates for TRIM proteins but also unexpectedly deep evolutionary connections between TRIM proteins and RNA Helicases, thereby linking ubiquitin and RNA biology throughout animal evolution.
Frances V Fullerpace - One of the best experts on this subject based on the ideXlab platform.
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looking back on the birth of dead box RNA Helicases
Biochimica et Biophysica Acta, 2013Co-Authors: Patrick Linder, Frances V FullerpaceAbstract:DEAD-box proteins represent the largest family of RNA Helicases, present in all three kingdoms of life. They are involved in a variety of processes involving RNA metabolism and in some instances also in processes that use guide RNAs. Since their first descriptions in the late 1980s, the perception of their molecular activities has dramatically changed. At the time when only eight proteins with 9 conserved motifs constituted the DEAD-box protein family, it was the biochemical characterization of mammalian eIF4A that first suggested a local unwinding activity. This was confirmed in vitro using partially double stranded RNA substrates with the unexpected result of a bidirectional unwinding activity. A real change of paradigm from the classical helicase activity to localized RNA unwinding occurred with the publication of the vasa•RNA structure with a bend in the RNA substrate and the insightful work from several laboratories demonstrating local unwinding without translocation. Finally, elegant work on the exon-junction complex revealed how DEAD-box proteins can bind to RNA to serve as clamps to function as nucleation centers to form RNP complexes. This article is part of a Special Issue entitled: The Biology of RNA Helicases - Modulation for life.
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RNA Helicases p68 and p72 multifunctional proteins with important implications for cancer development
Future Oncology, 2011Co-Authors: Frances V Fullerpace, Hayley C MooreAbstract:The DEAD box RNA Helicases p68 (DDX5) and p72 (DDX17) play important roles in multiple cellular processes that are commonly dysregulated in cancers, including transcription, pre-mRNA processing/alteRNAtive splicing and miRNA processing. Although p68 and p72 appear to have some overlapping functions, they clearly also have distinct, nonredundant functions. Furthermore, their ability to interact with a variety of different factors and act as multifunctional proteins has the potential to impact on several different processes, and alterations in expression or function of p68 and/or p72 could have profound implications for cancer development. However, their roles are likely to be context-dependent and both proteins have been reported to have pro-proliferation or even oncogenic functions as well as antiproliferative or tumor cosuppressor roles. Therefore, eludicating the precise role of these proteins in cancer is likely to be complex and to depend on the cellular environment and interacting factors. In this article, we review the many functions that have been attributed to p68 and p72 and discuss their potential roles in cancer development.
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the dead box RNA Helicases p68 ddx5 and p72 ddx17 novel transcriptional co regulators
Biochemical Society Transactions, 2008Co-Authors: Frances V Fullerpace, Simak AliAbstract:DEAD box [a motif named after its amino acid sequence (Asp-Glu-Ala-Asp)] RNA Helicases are known to play key roles in all cellular processes that require modulation of RNA structure. However, in recent years, several of these proteins have been found to function in transcriptional regulation. In the present paper, we shall review the literature demonstrating the action of p68 and, where data are available, p72 as transcriptional co-regulators for a range of transcription factors, namely ERα (oestrogen receptor α), the tumour suppressor p53, the myogenic regulator MyoD and Runx2, a transcription factor essential for osteoblast development. We shall also discuss evidence indicating that, in some cases at least, p68 and p72 have distinct, non-redundant, roles.
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dexd h box RNA Helicases multifunctional proteins with important roles in transcriptional regulation
Nucleic Acids Research, 2006Co-Authors: Frances V FullerpaceAbstract:The DExD/H box family of proteins includes a large number of proteins that play important roles in RNA metabolism. Members of this family have been shown to act as RNA Helicases or unwindases, using the energy from ATP hydrolysis to unwind RNA structures or dissociate RNA–protein complexes in cellular processes that require modulation of RNA structures. However, it is clear that several members of this family are multifunctional and, in addition to acting as RNA Helicases in processes such as pre-mRNA processing, play important roles in transcriptional regulation. In this review I shall concentrate on RNA helicase A (Dhx9), DP103 (Ddx20), p68 (Ddx5) and p72 (Ddx17), proteins for which there is a strong body of evidence showing that they play important roles in transcription, often as coactivators or corepressors through their interaction with key components of the transcriptional machinery, such as CREB-binding protein, p300, RNA polymerase II and histone deacetylases.
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the p68 and p72 dead box RNA Helicases interact with hdac1 and repress transcription in a promoter specific manner
BMC Molecular Biology, 2004Co-Authors: Brian J Wilson, Gaynor J Bates, David J Gregory, Neil D Perkins, Samantha M Nicol, Frances V FullerpaceAbstract:Background p68 (Ddx5) and p72 (Ddx17) are highly related members of the DEAD box family and are established RNA Helicases. They have been implicated in growth regulation and have been shown to be involved in both pre-mRNA and pre-rRNA processing. More recently, however, these proteins have been reported to act as transcriptional co-activators for estrogen-receptor alpha (ERα). Furthermore these proteins were shown to interact with co-activators p300/CBP and the RNA polymerase II holoenzyme. Taken together these reports suggest a role for p68 and p72 in transcriptional activation.
