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| Subject Categories: Chromatin & Transcription | Molecular Biology of Disease |
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| The EMBO Journal
(2007) 26, 3558–3569, doi:10.1038/sj.emboj.7601794 Published online 12 July 2007 |
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| Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma |
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| Sharmistha Pal1, Robert A Baiocchi2, John C Byrd2, Michael R Grever2, Samson T Jacob1 and Saïd Sif1 |
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1 Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, USA 2 Division of Hematology-Oncology, Department of Internal Medicine and College of Medicine, The Ohio State University, Columbus, OH, USA To whom correspondence should be addressed Saïd Sif, Department of Molecular and Cellular Biochemistry, Ohio State University College of Medicine, 1645 Neil Avenue, Columbus, OH 43210, USA. Tel.: +1 614 247 7445; Fax: +1 614 292 4118; E-mail: sif.1@osu.edu Received 3 January 2007; Accepted 13 June 2007; Published online 12 July 2007. |
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| Abstract |
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| Protein arginine methyltransferase PRMT5 interacts with human SWI/SNF complexes and methylates histones H3R8 and H4R3. To elucidate the role of PRMT5 in human cancer, we analyzed PRMT5 expression in normal human B lymphocytes and a panel of lymphoid cancer cell lines as well as mantle cell lymphoma (MCL) clinical samples. We show that PRMT5 protein levels are elevated in all cancer cells, including clinical samples examined despite its low rate of transcription and messenger RNA stability. Remarkably, polysome profiling revealed that PRMT5 mRNA is translated more efficiently in Mino and JeKo MCL cells than in normal B cells, and that decreased miR-92b and miR-96 expression augments PRMT5 translation. Consequently, global methylation of H3R8 and H4R3 is increased and is accompanied by repression of suppressor of tumorigenecity 7 (ST7) in lymphoid cancer cells. Furthermore, knockdown of PRMT5 expression reduces proliferation of transformed JeKo and Raji cells. Thus, our studies indicate that aberrant expression of PRMT5 leads to altered epigenetic modification of chromatin, which in turn impacts transcriptional performance of anti-cancer genes and growth of transformed lymphoid cells. |
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| Keywords: H3R8 and H4R3 methylation, mantle cell lymphoma, miR-92b and miR-96, PRMT5, ST7 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHJournal of Investigative Dermatology Letter Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma The EMBO Journal Article Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing Nature Genetics Article (01 Mar 2005) SKB1-mediated symmetric dimethylation of histone H4R3 controls flowering time in Arabidopsis The EMBO Journal Article (04 Apr 2007) |
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