Analysis of the Yeast Arginine Methyltransferase Hmt1p/Rmt1p and Its in Vivo Function

McBride, Anne; Weiss, Valerie H.; Kim, Heidi K.; Hogle, James M.; Silver, Pamela A.

doi:10.1074/jbc.275.5.3128

Cited by 90 publications

(109 citation statements)

References 45 publications

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“…As it is technically difficult to purify fulllength Axin, GST-fused N-terminus (amino acids 1-406) and C-terminus of Axin (amino acids 407-832) were used in in vitro methylation assays. As shown in Figure 2a, only wild-type (WT) GST-PRMT1 methylated the N-terminus of Axin, compared with dominantnegative GST-PRMT1 which has no enzymatic activity (McBride et al, 2000). PRMT1 is a type I arginine methyltransferase, a group that includes PRMT3, PRMT4/Carm1 and PRMT6 (Bedford and Clarke, 2009), and has several splicing variants (Goulet et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling

Cha

Kim

et al. 2011

Oncogene

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Axin, a negative regulator of Wnt signaling, is a key scaffold protein for the b-catenin destruction complex. It has been previously shown that multiple post-translational modification enzymes regulate the level of Axin. Here, we provide evidence that protein arginine methyltransferase 1 (PRMT1) directly interacts with and methylates the 378th arginine residue of Axin both in vitro and in vivo. We found that the transient expression of PRMT1 led to an increased level of Axin and that knockdown of endogenous PRMT1 by short hairpin RNA reduced the level of Axin. These results suggest that methylation by PRMT1 enhanced the stability of Axin. Methylation of Axin by PRMT1 also seemingly enhanced the interaction between Axin and glycogen synthase kinase 3b, leading to decreased ubiquitination of Axin. Consistent with the role of PRMT1 in the regulation of Axin, knockdown of PRMT1 enhanced the level of cytoplasmic b-catenin as well as b-catenin-dependent transcription activity. In summary, we show that the methylation of Axin occurred in vivo and controlled the stability of Axin. Therefore, methylation of Axin by PRMT1 may serve as a finely tuned regulation mechanism for Wnt/b-catenin signaling.

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Section: Resultsmentioning

confidence: 99%

Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling

Cha

Kim

et al. 2011

Oncogene

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“…1B) and a previously generated Hmt1 catalytic (G68R) mutant ( Fig. 1C; McBride et al 2000). We next sought to determine if the rate of rDNA mitotic recombination could be lowered by overexpressing Hmt1.…”

Section: Resultsmentioning

confidence: 99%

The role of protein arginine methylation in the formation of silent chromatin

Lamming²,

Eskin³

et al. 2006

Genes Dev.

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Establishment and maintenance of silent chromatin in the Saccharomyces cerevisiae involves a step-wise assembly of the SIR complex. Here we demonstrate a role for the protein arginine methyltransferase Hmt1 in this process. In the absence of catalytically active Hmt1, yeast cells display increased transcription from silent chromatin regions and increased mitotic recombination within tandem repeats of rDNA. At the molecular level, loss of Hmt1's catalytic activity results in decreased Sir2 and dimethylated Arg-3 histone H4 occupancy across silent chromatin regions. These data suggest a model whereby protein arginine methylation affects the establishment and maintenance of silent chromatin. Received April 11, 2006; revised version accepted October 23, 2006. In a eukaryotic cell, different chromosomal regions display varying degrees of transcriptional competency. This is the result of selective transcriptional repression or silencing that renders specific chromatin domains inaccessible to the transcriptional machinery. Analogous to metazoan heterochromatin, there are three chromosomal regions in the yeast Saccharomyces cerevisiae that are epigenetically transcriptionally silenced (Rusche et al. 2003); the telomeres, the silent mating loci (HMR and HML), and the rDNA loci. Within these regions are cisacting elements known as silencers and telomeric repeats that serve as nucleation points to recruit transacting proteins responsible for the establishment and maintenance of silent chromatin.One of the most prominent trans-acting proteins involved in the establishment and maintenance of silencing at these loci is Silent Information Regulator-2 (Sir2), an NAD + -dependent histone deacetylase (Blander and Guarente 2004). Sir2 plays a crucial role in the formation of silent chromatin. In addition, Sir2 is involved in the maintenance of genome stability via the repair of doublestranded DNA breaks by nonhomologous recombination. For example, Sir2 is recruited to sites of DNA strand breaks (Martin et al. 1999;Mills et al. 1999) and Sir2-dependent localized histone acetylation triggers the homologous recombination pathway of double-strand DNA repair (Tamburini and Tyler 2005).Sir2 forms complexes with different proteins to promote silencing. For example, the Sir1/2/3/4 complex functions to silence transcription at the mating-type loci, whereas a Sir2/3/4 complex mediates silencing at the telomeres (Kaeberlein et al. 1999). At the rDNA, Sir2 associates with Cdc14 and Net1 to form the RENT (regulator of the nucleolar silencing and telophase exit) complex (Ghidelli et al. 2001). These complexes are thought to promote the formation of silent chromatin through stepwise propagation along the DNA (Hoppe et al. 2002).Arginine methylation is a post-translational modification commonly found in nucleic acid-binding proteins (Bedford and Richard 2005). The enzyme that catalyzes this modification belongs to a growing enzyme family called protein arginine methyltransferases or PRMTs. Arginine residues may be either monomethylated or di...

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“…It is comprised of three RNA recognition motifs and one serine/arginine-rich domain with 10 SR or RS motifs. This SR domain contains also two arginine/glycine/ glycine (RGG) motifs, which for Npl3 have been shown previously to be substrates for arginine methylation by the arginine methyltransferase Hmt1 (31)(32)(33)(34).…”

Section: Hrb1 Is a Nuclear Sr-type Protein That Requires The Karyophementioning

confidence: 99%

Differential Export Requirements for Shuttling Serine/Arginine-type mRNA-binding Proteins

Häcker

Krebber

2004

Journal of Biological Chemistry

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Messenger RNAs are transported to the cytoplasm bound to several shuttling mRNA-binding proteins. Here, we present the characterization of Hrb1, a novel component of the transported ribonucleoprotein complex in Saccharomyces cerevisiae. The protein is similar to the other two serine/arginine (SR)-type proteins in yeast, Gbp2 and Npl3. Hrb1 is nuclear at steady state and its import is mediated by the karyopherin Mtr10. Hrb1 binds to poly(A)؉ RNA in vivo and its binding is significantly increased in MTR10 mutants, suggesting a role for Mtr10 in dissociating Hrb1 from the mRNAs. Interestingly, by comparing the export requirements of all three SR proteins we find similarities but also striking differences. While the export of all three proteins is dependent on the export of mRNAs in general, as no transport is observed in mutants defective in transcription (rpb1-1) or mRNA export (mex67-5), we find specific requirements for components of the THO complex, involved in transcription elongation. While both Hrb1 and Gbp2 depend on Mft1 and Hpr1 for their nuclear export, Npl3 is exported independently of both proteins. These findings suggest that Hrb1 and Gbp2, but not Npl3, might be loaded onto the growing mRNA via the THO complex components Mtf1 and Hrp1.

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Analysis of the Yeast Arginine Methyltransferase Hmt1p/Rmt1p and Its in Vivo Function

Cited by 90 publications

References 45 publications

Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling

Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling

The role of protein arginine methylation in the formation of silent chromatin

Differential Export Requirements for Shuttling Serine/Arginine-type mRNA-binding Proteins

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