Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins

Gonsalvez, Graydon B.; Tian, Liang; Ospina, Jason K.; Boisvert, François-Michel; Lamond, Angus I.; Matera, A. Gregory

doi:10.1083/jcb.200702147

Cited by 132 publications

(124 citation statements)

References 33 publications

(61 reference statements)

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“…28,2008 PRMT5 SUPPRESSES RBL2 GENE EXPRESSION 6263 incubated in 3 ml of RPMI 1640 containing 10% FBS, and whole-cell extracts were prepared 30 h later in 100 l of radioimmunoprecipitation assay lysis buffer before PRMT5 and pocket proteins were detected by Western blotting. Primers used to generate wild-type and mutant miR-92b and miR-96 dsRNAs were described previously (30 To knock down the expression of PRMT5 and RBL2, T7-driven single-stranded DNA oligonucleotides were generated according to previously published sequences (3,15). Chromatin immunoprecipitation (ChIP) assay.…”

Section: Methodsmentioning

confidence: 99%

Protein Arginine Methyltransferase 5 Suppresses the Transcription of the RB Family of Tumor Suppressors in Leukemia and Lymphoma Cells

Wang

Pal

Sif

2008

Molecular and Cellular Biology

233

225

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The proper epigenetic modification of chromatin by protein arginine methyltransferases (PRMTs) is crucial for normal cell growth and health. The human SWI/SNF-associated PRMT5 is involved in the transcriptional repression of target genes by directly methylating H3R8 and H4R3. To further understand the impact of PRMT5-mediated histone methylation on cancer, we analyzed its expression in normal and transformed human B lymphocytes. Our findings reveal that PRMT5 protein levels are enhanced in various human lymphoid cancer cells, including transformed chronic lymphocytic leukemia (B-CLL) cell lines. PRMT5 overexpression is caused by the altered expression of the PRMT5-specific microRNAs 19a, 25, 32, 92, 92b, and 96 and results in the increased global symmetric methylation of H3R8 and H4R3. An evaluation of both epigenetic marks at PRMT5 target genes such as RB1 (p105), RBL1 (p107), and RBL2 (p130) showed that promoters H3R8 and H4R3 are hypermethylated, which in turn triggers pocket protein transcriptional repression. Furthermore, reducing PRMT5 expression in WaC3CD5 B-CLL cells abolishes H3R8 and H4R3 hypermethylation, restores RBL2 expression, and inhibits cancer cell proliferation. These results indicate that PRMT5 overexpression epigenetically alters the transcription of key tumor suppressor genes and suggest a causal role of the elevated symmetric methylation of H3R8 and H4R3 at the RBL2 promoter in transformed B-lymphocyte pathology.Enzymes that modify chromatin via arginine methylation have different effects on gene expression, depending on whether they catalyze either the symmetric or asymmetric dimethylation of histones (20,31). Recent work has clearly established a link between the aberrant expression of chromatinmodifying enzymes and cancer; however, the impact protein arginine methyltransferases (PRMTs) have on cell growth and proliferation has only begun to be appreciated. The role PRMTs play in cancer epigenetics remains unexplored, and it is essential to unravel how histone arginine methylation influences cancer. Previous studies have shown that the expression of EZH2, the catalytic subunit of PRC2/3, is altered in cancer cells (19,32,40,41). Similarly, several reports have shown that the interplay and cross-talk between chromatin-modifying enzymes is necessary for the efficient regulation of gene expression, and that changes that affect the activity and/or targeting of chromatin remodelers can trigger cancer (13, 23).Histone methylation has emerged as an important epigenetic modification in the control of chromatin structure and gene expression, and there is little doubt that different epigenetic marks act either synergistically or antagonistically to specify transcriptional performance in various chromatin regions (13). The methylation of histones can be found on both lysine and arginine residues, and both modifications are introduced by SET and PRMT enzymes, respectively. Just like SET proteins, which either can induce or repress transcription, PRMTs either can induce or inhibit transcription depen...

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Section: Methodsmentioning

confidence: 99%

Protein Arginine Methyltransferase 5 Suppresses the Transcription of the RB Family of Tumor Suppressors in Leukemia and Lymphoma Cells

Wang

Pal

Sif

2008

Molecular and Cellular Biology

233

225

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“…14,89,90 Cells lacking 5 0 -methylthioadenosine phosphorylase, a key enzyme of the methionine salvage pathway, have reduced methylation activity and coilin is re-localized to nucleoli. 91 However, this result has to be cautiously interpreted because 2 methyltransferases, PRMT5 and PRMT7, that symmetrically methylate arginines in Sm proteins, are important for snRNP biogenesis 92 and ongoing snRNP biogenesis may be critical for CB formation. 93,94 Coilin is also heavily phosphorylated and phosphorylation controls CB disassembly at mitosis, proper CB assembly after mitosis and coilin localization.…”

Section: Post-transcriptional Modificationsmentioning

confidence: 99%

Coilin: The first 25 years

2015

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“…In vivo, PRMT7 has been found to interact with the mammalian testis-specific CCTC-binding factor-like protein to control genetic imprinting (19). In addition, PRMT7 methylated the Sm proteins that constitute the spliceosome and seemed to mediate RNA splicing (20). It was also suggested that PRMT7 was associated with sensitivity to a number of DNA damage agents (21)(22)(23).…”

mentioning

confidence: 99%

Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription

Ying

Mei

Zhang

et al. 2015

The Journal of Immunology

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B cells are the center of humoral immunity and produce Abs to protect against foreign Ags. B cell defects lead to diseases such as leukemia and lymphomas. Histone arginine methylation is important for regulating gene activation and silencing in cells. Although the process commonly exists in mammalian cells, its roles in B cells are unknown. To explore the effects of aberrant histone arginine methylation on B cells, we generated mice with a B cell–specific knockout of PRMT7, a member of the methyltransferases that mediate arginine methylation of histones. In this article, we showed that the loss of PRMT7 led to decreased mature marginal zone B cells and increased follicular B cells and promoted germinal center formation after immunization. Furthermore, mice lacking PRMT7 expression in B cells secreted low levels of IgG1 and IgA. Abnormal expression of germinal center genes (i.e., Bcl6, Prdm1, and Irf4) was detected in conditional knockout mice. By overexpressing PRMT7 in the Raji and A20 cell lines derived from B cell lymphomas, we validated the fact that PRMT7 negatively regulated Bcl6 expression. Using chromatin immunoprecipitation–PCR, we found that PRMT7 could recruit H4R3me1 and symmetric H4R3me2 to the Bcl6 promoter. These results provide evidence for the important roles played by PRMT7 in germinal center formation.

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Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins

Cited by 132 publications

References 33 publications

Protein Arginine Methyltransferase 5 Suppresses the Transcription of the RB Family of Tumor Suppressors in Leukemia and Lymphoma Cells

Protein Arginine Methyltransferase 5 Suppresses the Transcription of the RB Family of Tumor Suppressors in Leukemia and Lymphoma Cells

Coilin: The first 25 years

Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription

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