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https://www.readbyqxmd.com/read/26214185/the-stability-of-ribosome-biogenesis-factor-wbscr22-is-regulated-by-interaction-with-trmt112-via-ubiquitin-proteasome-pathway
#1
Kadri Õunap, Lilian Leetsi, Maarja Matsoo, Reet Kurg
The human WBSCR22 protein is a 18S rRNA methyltransferase involved in pre-rRNA processing and ribosome 40S subunit biogenesis. Recent studies have shown that the protein function in ribosome synthesis is independent of its enzymatic activity. In this work, we have studied the WBSCR22 protein interaction partners by SILAC-coupled co-immunoprecipitation assay and identified TRMT112 as the interaction partner of WBSCR22. Knock-down of TRMT112 expression decreased the WBSCR22 protein level in mammalian cells, suggesting that the stability of WBSCR22 is regulated through the interaction with TRMT112...
2015: PloS One
https://www.readbyqxmd.com/read/25851604/the-human-18s-rrna-base-methyltransferases-dimt1l-and-wbscr22-trmt112-but-not-rrna-modification-are-required-for-ribosome-biogenesis
#2
Christiane Zorbas, Emilien Nicolas, Ludivine Wacheul, Emmeline Huvelle, Valérie Heurgué-Hamard, Denis L J Lafontaine
At the heart of the ribosome lie rRNAs, whose catalytic function in translation is subtly modulated by posttranscriptional modifications. In the small ribosomal subunit of budding yeast, on the 18S rRNA, two adjacent adenosines (A1781/A1782) are N(6)-dimethylated by Dim1 near the decoding site, and one guanosine (G1575) is N(7)-methylated by Bud23-Trm112 at a ridge between the P- and E-site tRNAs. Here we establish human DIMT1L and WBSCR22-TRMT112 as the functional homologues of yeast Dim1 and Bud23-Trm112...
June 1, 2015: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/25525153/wbscr22-merm1-is-required-for-late-nuclear-pre-ribosomal-rna-processing-and-mediates-n7-methylation-of-g1639-in-human-18s-rrna
#3
Sara Haag, Jens Kretschmer, Markus T Bohnsack
Ribosomal (r)RNAs are extensively modified during ribosome synthesis and their modification is required for the fidelity and efficiency of translation. Besides numerous small nucleolar RNA-guided 2'-O methylations and pseudouridinylations, a number of individual RNA methyltransferases are involved in rRNA modification. WBSCR22/Merm1, which is affected in Williams-Beuren syndrome and has been implicated in tumorigenesis and metastasis formation, was recently shown to be involved in ribosome synthesis, but its molecular functions have remained elusive...
February 2015: RNA
https://www.readbyqxmd.com/read/25489090/structural-and-functional-studies-of-bud23-trm112-reveal-18s-rrna-n7-g1575-methylation-occurs-on-late-40s-precursor-ribosomes
#4
Juliette Létoquart, Emmeline Huvelle, Ludivine Wacheul, Gabrielle Bourgeois, Christiane Zorbas, Marc Graille, Valérie Heurgué-Hamard, Denis L J Lafontaine
The eukaryotic small ribosomal subunit carries only four ribosomal (r) RNA methylated bases, all close to important functional sites. N(7)-methylguanosine (m(7)G) introduced at position 1575 on 18S rRNA by Bud23-Trm112 is at a ridge forming a steric block between P- and E-site tRNAs. Here we report atomic resolution structures of Bud23-Trm112 in the apo and S-adenosyl-L-methionine (SAM)-bound forms. Bud23 and Trm112 interact through formation of a β-zipper involving main-chain atoms, burying an important hydrophobic surface and stabilizing the complex...
December 23, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25352209/knockdown-of-merm1-wbscr22-attenuates-sensitivity-of-h460-non-small-cell-lung-cancer-cells-to-sn-38-and-5-fu-without-alteration-to-p53-expression-levels
#5
Dongmei Yan, Xiaoliang Zheng, Linglan Tu, Jing Jia, Qin Li, Liyan Cheng, Xiaoju Wang
Merm1/Wbscr22 is a novel metastasis promoter that has been shown to be involved in tumor metastasis, viability and apoptosis. To the best of our knowledge, there are currently no studies suggesting the possible correlation between the expression of Merm1/Wbscr22 in tumor cells and chemosensitivity to antitumor agents. In the present study, two human non-small cell lung cancer cell lines, H1299 and H460, were used to investigate whether Merm1/Wbscr22 affects chemosensitivity to antitumor agents, including cisplatin (CDDP), doxorubicin (ADM), paclitaxel (PTX), mitomycin (MMC), 7-Ethyl-10-hydroxycamptothecin (SN-38; the active metabolite of camptothecin) and 5-fluorouracil (5-FU)...
January 2015: Molecular Medicine Reports
https://www.readbyqxmd.com/read/24763612/genome-wide-study-of-hypomethylated-and-induced-genes-in-patients-with-liver-cancer-unravels-novel-anticancer-targets
#6
Barbara Stefanska, David Cheishvili, Matthew Suderman, Ani Arakelian, Jian Huang, Michael Hallett, Ze-Guang Han, Mamun Al-Mahtab, Sheikh Mohammad Fazle Akbar, Wasif Ali Khan, Rubhana Raqib, Imrana Tanvir, Haseeb Ahmed Khan, Shafaat A Rabbani, Moshe Szyf
PURPOSE: We utilized whole-genome mapping of promoters that are activated by DNA hypomethylation in hepatocellular carcinoma (HCC) clinical samples to shortlist novel targets for anticancer therapeutics. We provide a proof of principle of this approach by testing six genes short-listed in our screen for their essential role in cancer growth and invasiveness. EXPERIMENTAL DESIGN: We used siRNA- or shRNA-mediated depletion to determine whether inhibition of these genes would reduce human tumor xenograft growth in mice as well as cell viability, anchorage-independent growth, invasive capacities, and state of activity of nodal signaling pathways in liver, breast, and bladder cancer cell lines...
June 15, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/24488492/the-methyltransferase-wbscr22-merm1-enhances-glucocorticoid-receptor-function-and-is-regulated-in-lung-inflammation-and-cancer
#7
Maryam Jangani, Toryn M Poolman, Laura Matthews, Nan Yang, Stuart N Farrow, Andrew Berry, Neil Hanley, Andrew J K Williamson, Anthony D Whetton, Rachelle Donn, David W Ray
Glucocorticoids (GC) regulate cell fate and immune function. We identified the metastasis-promoting methyltransferase, metastasis-related methyltransferase 1 (WBSCR22/Merm1) as a novel glucocorticoid receptor (GR) regulator relevant to human disease. Merm1 binds the GR co-activator GRIP1 but not GR. Loss of Merm1 impaired both GR transactivation and transrepression by reducing GR recruitment to its binding sites. This was accompanied by loss of GR-dependent H3K4Me3 at a well characterized promoter. Inflammation promotes GC resistance, in part through the actions of TNFα and IFNγ...
March 28, 2014: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24086612/the-human-wbscr22-protein-is-involved-in-the-biogenesis-of-the-40s-ribosomal-subunits-in-mammalian-cells
#8
Kadri Õunap, Ly Käsper, Ants Kurg, Reet Kurg
The human WBSCR22 protein was previously shown to be up-regulated in invasive breast cancer and its ectopic expression enhances tumor cell survival in the vasculature. In the current study, we show that the WBSCR22 protein is important for cell growth. Knock-down of WBSCR22 with siRNA results in slower growth of WBSCR22-depleted cells. Treatment with siWBSCR22 causes defects in the processing of pre-rRNAs and reduces the level of free 40S ribosomal subunit, suggesting that WBSCR22 is involved in ribosome small subunit biosynthesis...
2013: PloS One
https://www.readbyqxmd.com/read/22147262/identification-of-molecular-vulnerabilities-in-human-multiple-myeloma-cells-by-rna-interference-lethality-screening-of-the-druggable-genome
#9
Rodger E Tiedemann, Yuan Xao Zhu, Jessica Schmidt, Chang Xin Shi, Chris Sereduk, Hongwei Yin, Spyro Mousses, A Keith Stewart
Despite recent advances in targeted treatments for multiple myeloma, optimal molecular therapeutic targets have yet to be identified. To functionally identify critical molecular targets, we conducted a genome-scale lethality study in multiple myeloma cells using siRNAs. We validated the top 160 lethal hits with four siRNAs per gene in three multiple myeloma cell lines and two non-myeloma cell lines, cataloging a total of 57 potent multiple myeloma survival genes. We identified the Bcl2 family member MCL1 and several 26S proteasome subunits among the most important and selective multiple myeloma survival genes...
February 1, 2012: Cancer Research
https://www.readbyqxmd.com/read/21148752/the-novel-metastasis-promoter-merm1-wbscr22-enhances-tumor-cell-survival-in-the-vasculature-by-suppressing-zac1-p53-dependent-apoptosis
#10
Youya Nakazawa, Hiroyuki Arai, Naoya Fujita
Understanding metastasis is integral to curative cancer treatments. Using a mouse genetic screening model, we identified Merm1/Wbscr22 as a novel metastasis promoter that includes a methyltransferase fold in its structure. Merm1 showed high levels of expression in invasive breast cancer. Ectopic expression of Merm1 in nonmetastatic cells enhanced metastasis formation without affecting cell growth and motility. The intact methyltransferase fold of Merm1 was required for metastasis formation. Interestingly, Merm1 expression promoted cell survival after entrapment in the lung microvasculature...
February 1, 2011: Cancer Research
https://www.readbyqxmd.com/read/12073013/identification-of-additional-transcripts-in-the-williams-beuren-syndrome-critical-region
#11
Giuseppe Merla, Catherine Ucla, Michel Guipponi, Alexandre Reymond
Williams-Beuren syndrome (WBS) is a developmental disorder associated with haploinsufficiency of multiple genes at 7q11.23. Here, we report the characterization of WBSCR16, WBSCR17, WBSCR18, WBSCR20A, WBSCR20B, WBSCR20C, WBSCR21, WBSCR22, and WBSCR23, nine novel genes contained in the WBS commonly deleted region or its flanking sequences. They encode an RCC1-like G-exchanging factor, an N-acetylgalactosaminyltransferase, a DNAJ-like chaperone, NOL1/NOP2/sun domain-containing proteins, a methyltransferase, or proteins with no known homologies...
May 2002: Human Genetics
https://www.readbyqxmd.com/read/11978965/characterization-of-two-novel-genes-wbscr20-and-wbscr22-deleted-in-williams-beuren-syndrome
#12
A Doll, K H Grzeschik
Williams-Beuren syndrome (WBS), due to a contiguous gene deletion of approximately 1.5 Mb at 7q11.23, is a complex developmental disorder with multisystemic manifestations including supravalvular aortic stenosis (SVAS) and a specific cognitive phenotype. Large repeats containing genes and pseudogenes flank the deletion breakpoints, and the mutation mechanism commonly appears to be unequal meiotic crossover. Except for elastin, hemizygosity of which is associated with supravalvular aortic stenosis, it is unknown which of the 18 genes in the deletion area contributes to the phenotype...
2001: Cytogenetics and Cell Genetics
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