The Experts below are selected from a list of 6963 Experts worldwide ranked by ideXlab platform
Michaeala Frye - One of the best experts on this subject based on the ideXlab platform.
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the nucleolar rna methyltransferase misu nSUN2 is required for mitotic spindle stability
Journal of Cell Biology, 2009Co-Authors: Sandra Blanco Benavente, Agata Kurowski, Elisabete Nascimento, Ilaria Dragoni, Astrid Gillich, Peter Humphreys, Michaeala FryeAbstract:Myc-induced SUN Domain–containing protein (Misu or NSUN2) is a nucleolar RNA methyltransferase important for c-Myc–induced proliferation in skin, but the mechanisms by which Misu contributes to cell cycle progression are unknown. In this study, we demonstrate that Misu translocates from the nucleoli in interphase to the spindle in mitosis as an RNA–protein complex that includes 18S ribosomal RNA. Functionally, depletion of Misu caused multiple mitotic defects, including formation of unstructured spindles, multipolar spindles, and chromosome missegregation, leading to aneuploidy and cell death. The presence of both RNA and Misu is required for correct spindle assembly, and this process is independent of active translation. Misu might mediate its function at the spindle by recruiting nucleolar and spindle-associated protein (NuSAP), an essential microtubule-stabilizing and bundling protein. We further identify NuSAP as a novel direct target gene of c-Myc. Collectively, our results suggest a novel mechanism by which c-Myc promotes proliferation by stabilizing the mitotic spindle in fast-dividing cells via Misu and NuSAP.
Markus T Bohnsack - One of the best experts on this subject based on the ideXlab platform.
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eukaryotic 5 methylcytosine m c rna methyltransferases mechanisms cellular functions and links to disease
Genes, 2019Co-Authors: Katherine E Bohnsack, Claudia Hobartner, Markus T BohnsackAbstract:5-methylcytosine (m5C) is an abundant RNA modification that’s presence is reported in a wide variety of RNA species, including cytoplasmic and mitochondrial ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs), as well as messenger RNAs (mRNAs), enhancer RNAs (eRNAs) and a number of non-coding RNAs. In eukaryotes, C5 methylation of RNA cytosines is catalyzed by enzymes of the NOL1/NOP2/SUN Domain (NSUN) family, as well as the DNA methyltransferase homologue DNMT2. In recent years, substrate RNAs and modification target nucleotides for each of these methyltransferases have been identified, and structural and biochemical analyses have provided the first insights into how each of these enzymes achieves target specificity. Functional characterizations of these proteins and the modifications they install have revealed important roles in diverse aspects of both mitochondrial and nuclear gene expression. Importantly, this knowledge has enabled a better understanding of the molecular basis of a number of diseases caused by mutations in the genes encoding m5C methyltransferases or changes in the expression level of these enzymes.
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eukaryotic 5 methylcytosine m5c rna methyltransferases mechanisms cellular functions and links to disease
Genes, 2019Co-Authors: Katherine E Bohnsack, Claudia Hobartner, Markus T BohnsackAbstract:5-methylcytosine (m5C) is an abundant RNA modification that’s presence is reported in a wide variety of RNA species, including cytoplasmic and mitochondrial ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs), as well as messenger RNAs (mRNAs), enhancer RNAs (eRNAs) and a number of non-coding RNAs. In eukaryotes, C5 methylation of RNA cytosines is catalyzed by enzymes of the NOL1/NOP2/SUN Domain (NSUN) family, as well as the DNA methyltransferase homologue DNMT2. In recent years, substrate RNAs and modification target nucleotides for each of these methyltransferases have been identified, and structural and biochemical analyses have provided the first insights into how each of these enzymes achieves target specificity. Functional characterizations of these proteins and the modifications they install have revealed important roles in diverse aspects of both mitochondrial and nuclear gene expression. Importantly, this knowledge has enabled a better understanding of the molecular basis of a number of diseases caused by mutations in the genes encoding m5C methyltransferases or changes in the expression level of these enzymes.
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nSUN6 is a human rna methyltransferase that catalyzes formation of m5c72 in specific trnas
RNA, 2015Co-Authors: Sara Haag, Ahmed S Warda, Manuel A Gunnigmann, Claudia Hobartner, Jens Kretschmer, Markus T BohnsackAbstract:Many cellular RNAs require modification of specific residues for their biogenesis, structure, and function. 5-methylcytosine (m5C) is a common chemical modification in DNA and RNA but in contrast to the DNA modifying enzymes, only little is known about the methyltransferases that establish m5C modifications in RNA. The putative RNA methyltransferase NSUN6 belongs to the family of Nol1/Nop2/SUN Domain (NSUN) proteins, but so far its cellular function has remained unknown. To reveal the target spectrum of human NSUN6, we applied UV crosslinking and analysis of cDNA (CRAC) as well as chemical crosslinking with 5-azacytidine. We found that human NSUN6 is associated with tRNAs and acts as a tRNA methyltransferase. Furthermore, we uncovered tRNACys and tRNAThr as RNA substrates of NSUN6 and identified the cytosine C72 at the 3′ end of the tRNA acceptor stem as the target nucleoside. Interestingly, target recognition in vitro depends on the presence of the 3′-CCA tail. Together with the finding that NSUN6 localizes to the cytoplasm and largely colocalizes with marker proteins for the Golgi apparatus and pericentriolar matrix, our data suggest that NSUN6 modifies tRNAs in a late step in their biogenesis.
Min Han - One of the best experts on this subject based on the ideXlab platform.
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kash protein syne 2 nesprin 2 and SUN proteins SUN1 2 mediate nuclear migration during mammalian retinal development
Human Molecular Genetics, 2011Co-Authors: Kai Lei, Yuan Zhuang, Min Han, Min Zhou, Cheryl M CraftAbstract:Nuclear movement relative to cell bodies is a fundamental process during certain aspects of mammalian retinal development. During the generation of photoreceptor cells in the cell division cycle, the nuclei of progenitors oscillate between the apical and basal surfaces of the neuroblastic layer (NBL). This process is termed interkinetic nuclear migration (INM). Furthermore, newly formed photoreceptor cells migrate and form the outer nuclear layer (ONL). In the current study, we demonstrated that a KASH Domain-containing protein, Syne-2/Nesprin-2, as well as SUN Domain-containing proteins, SUN1 and SUN2, play critical roles during INM and photoreceptor cell migration in the mouse retina. A deletion mutation of Syne-2/Nesprin-2 or double mutations of SUN1 and SUN2 caused severe reduction of the thickness of the ONL, mislocalization of photoreceptor nuclei and profound electrophysiological dysfunction of the retina characterized by a reduction of a- and b-wave amplitudes. We also provide evidence that Syne-2/Nesprin-2 forms complexes with either SUN1 or SUN2 at the nuclear envelope to connect the nucleus with dynein/dynactin and kinesin molecular motors during the nuclear migrations in the retina. These key retinal developmental signaling results will advance our understanding of the mechanism of nuclear migration in the mammalian retina.
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SUN1 2 and syne nesprin 1 2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice
Neuron, 2009Co-Authors: Xiaochang Zhang, Xiaobing Yuan, Yuan Zhuang, Min Han, Kai LeiAbstract:Nuclear movement is critical during neurogenesis and neuronal migration, which are fundamental for mammalian brain development. Although dynein, Lis1, and other cytoplasmic proteins are known for their roles in connecting microtubules to the nucleus during interkinetic nuclear migration (INM) and nucleokinesis, the factors connecting dynein/Lis1 to the nuclear envelope (NE) remain to be determined. We report here that the SUN-Domain proteins SUN1 and SUN2 and the KASH-Domain proteins Syne-1/Nesprin-1 and Syne-2/Nesprin-2 play critical roles in neurogenesis and neuronal migration in mice. We show that SUN1 and SUN2 redundantly form complexes with Syne-2 to mediate the centrosome-nucleus coupling during both INM and radial neuronal migration in the cerebral cortex. Syne-2 is connected to the centrosome through interactions with both dynein/dynactin and kinesin complexes. Syne-2 mutants also display severe defects in learning and memory. These results fill an important gap in our understanding of the mechanism of nuclear movement during brain development.
Michaela Frye - One of the best experts on this subject based on the ideXlab platform.
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JCB: ARTICLE The nucleolar RNA methyltransferase Misu (NSUN2) is required for mitotic spindle stability
2013Co-Authors: Shobbir Hussain, Agata Kurowski, Elisabete Nascimento, Ilaria Dragoni, Astrid Gillich, Peter Humphreys, Ra Blanco Benavente, Michaela FryeAbstract:Myc-induced SUN Domain–containing protein (Misu or NSUN2) is a nucleolar RNA methyltransferase important for c-Myc–induced proliferation in skin, but the mechanisms by which Misu contributes to cell cycle progression are unknown. In this study, we demonstrate that Misu translocates from the nucleoli in interphase to the spindle in mitosis as an RNA–protein complex that includes 18S ribosomal RNA. Functionally, depletion of Misu caused multiple mitotic defects, including formation of unstructured spindles, multipolar spindles, and chromosome missegregation
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the rna methyltransferase misu nSUN2 mediates myc induced proliferation and is upregulated in tumors
Current Biology, 2006Co-Authors: Michaela Frye, Fiona M WattAbstract:Summary Background Myc is a well-known proto-oncogene, but its functions in normal tissue remain enigmatic. In adult epidermis, Myc stimulates exit from the stem cell compartment, decreasing cell adhesion and, by an unknown mechanism, triggering proliferation of transit-amplifying cells. Results We describe a novel direct target gene of Myc, Misu, that is expressed at low levels in normal epidermis but is upregulated on Myc activation. Misu encodes a previously uncharacterized RNA methyltransferase with high sequence homology to NSUN2 and defines a new family of mammalian SUN-Domain-containing proteins. The nucleolar localization of Misu is dependent on RNA polymerase III transcripts, and knockdown of Misu decreases nucleolar size. In G2 phase of the cell cycle, Misu is found in cytoplasmic vesicles, and it decorates the spindle in mitosis. Misu expression is highest in S phase, and RNAi constructs block Myc-induced keratinocyte proliferation and cell-cycle progression. Misu is expressed at low levels in normal tissues, but is highly induced in a range of tumors. Growth of human squamous-cell-carcinoma xenografts is decreased by Misu RNAi. Conclusions Misu is a novel downstream Myc target that methylates RNA polymerase III transcripts. Misu mediates Myc-induced cell proliferation and growth and is a potential target for cancer therapies.
Sandra Blanco Benavente - One of the best experts on this subject based on the ideXlab platform.
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the nucleolar rna methyltransferase misu nSUN2 is required for mitotic spindle stability
Journal of Cell Biology, 2009Co-Authors: Sandra Blanco Benavente, Agata Kurowski, Elisabete Nascimento, Ilaria Dragoni, Astrid Gillich, Peter Humphreys, Michaeala FryeAbstract:Myc-induced SUN Domain–containing protein (Misu or NSUN2) is a nucleolar RNA methyltransferase important for c-Myc–induced proliferation in skin, but the mechanisms by which Misu contributes to cell cycle progression are unknown. In this study, we demonstrate that Misu translocates from the nucleoli in interphase to the spindle in mitosis as an RNA–protein complex that includes 18S ribosomal RNA. Functionally, depletion of Misu caused multiple mitotic defects, including formation of unstructured spindles, multipolar spindles, and chromosome missegregation, leading to aneuploidy and cell death. The presence of both RNA and Misu is required for correct spindle assembly, and this process is independent of active translation. Misu might mediate its function at the spindle by recruiting nucleolar and spindle-associated protein (NuSAP), an essential microtubule-stabilizing and bundling protein. We further identify NuSAP as a novel direct target gene of c-Myc. Collectively, our results suggest a novel mechanism by which c-Myc promotes proliferation by stabilizing the mitotic spindle in fast-dividing cells via Misu and NuSAP.
