Regulation of the Nuclear Poly(A)-binding Protein by Arginine Methylation in Fission Yeast

Perreault, Audrey; Lemieux, Carole; Bachand, François

doi:10.1074/jbc.m610512200

Cited by 60 publications

(102 citation statements)

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“…3). The specific role of the nuclear exosome in the negative regulation of meiotic genes is consistent with the nuclear localization of Pab2 (53) and Mmi1 (5). Interestingly, genome-wide localization analyses in budding yeast indicate the recruitment of exosome components to meiotic introncontaining genes (54), suggesting that the role of the exosome in the negative regulation of meiotic gene expression is conserved between fission and budding yeasts.…”

Section: Discussionsupporting

confidence: 71%

Negative Regulation of Meiotic Gene Expression by the Nuclear Poly(a)-binding Protein in Fission Yeast

St-André

Lemieux

Perreault

et al. 2010

Journal of Biological Chemistry

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105

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Meiosis is a cellular differentiation process in which hundreds of genes are temporally induced. Because the expression of meiotic genes during mitosis is detrimental to proliferation, meiotic genes must be negatively regulated in the mitotic cell cycle. Yet, little is known about mechanisms used by mitotic cells to repress meiosis-specific genes. Here we show that the poly(A)-binding protein Pab2, the fission yeast homolog of mammalian PABPN1, controls the expression of several meiotic transcripts during mitotic division. Our results from chromatin immunoprecipitation and promoter-swapping experiments indicate that Pab2 controls meiotic genes post-transcriptionally. Consistently, we show that the nuclear exosome complex cooperates with Pab2 in the negative regulation of meiotic genes. We also found that Pab2 plays a role in the RNA decay pathway orchestrated by Mmi1, a previously described factor that functions in the post-transcriptional elimination of meiotic transcripts. Our results support a model in which Mmi1 selectively targets meiotic transcripts for degradation via Pab2 and the exosome. Our findings have therefore uncovered a mode of gene regulation whereby a poly(A)-binding protein promotes RNA degradation in the nucleus to prevent untimely expression.Meiosis is a key differentiation process essential for the generation of genetically distinct individuals. During yeast meiosis, two cells of opposite mating types fuse and conjugate their DNA to form a diploid cell. This diploid cell undergoes DNA replication followed by two rounds of cell division to produce four haploid cells. Although many of the activities used to achieve cell division are common to both meiosis and mitosis, there are several features unique to meiosis. Importantly, the meiotic and mitotic cell cycles are mutually exclusive, and genes required for meiotic differentiation are solely expressed during meiosis. Such negative control of meiotic genes during mitosis suggests important regulatory systems to avoid inappropriate activation of meiosis. To date, however, the molecular mechanisms by which meiotic differentiation genes are suppressed during the mitotic cell cycle remain poorly understood.In the fission yeast Schizosaccharomyces pombe, meiotic differentiation involves the temporal activation of hundreds of genes (1). Although previous studies have established the importance of transcriptional regulation during fission yeast meiosis (1, 2), recent results implicate post-transcriptional mechanisms of gene regulation, including pre-mRNA splicing and mRNA degradation. Accordingly, several meiotic genes are specifically spliced during meiosis, but remain unspliced during the mitotic cell cycle (3, 4). Selective mRNA turnover is another mechanism used by fission yeast to ensure the absence of meiosis-specific transcripts during the mitotic cell cycle. The rapid elimination of specific meiotic transcripts in mitotic cells requires the YTH-family RNA-binding protein, Mmi1 (5). Mmi1 promotes the destruction of specific meiotic transcripts...

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Section: Discussionsupporting

confidence: 71%

Negative Regulation of Meiotic Gene Expression by the Nuclear Poly(a)-binding Protein in Fission Yeast

St-André

Lemieux

Perreault

et al. 2010

Journal of Biological Chemistry

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105

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“…Moreover, another nuclear RNA-binding protein with specificity to poly(A), Nab2, contributes to the regulation of poly(A) tail synthesis in this organism. 45,46 The recent identification of Pab2, 47 the S. pombe ortholog of PABPN1, is interesting and should provide powerful biochemical and genetic tools to study the cellular function of the nuclear PABP. Notably, pab2-null cells are viable and display hyperadenylated RNAs, suggesting that factors other than Pab2 can stimulate PAP processivity in fission yeast.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, pab2-null cells are viable and display hyperadenylated RNAs, suggesting that factors other than Pab2 can stimulate PAP processivity in fission yeast. 47 Recent microarrays experiments revealed that the abundance of most mRNAs is unaffected by the deletion of pab2 and that 3' end decision and mRNA poly(A) tails are similar to normal cells. 48 Unexpectedly, the deletion of pab2 led to the accumulation of polyadenylated small nucleolar RNAs (snoRNAs), 48 noncoding RNAs that assemble into ribonucleoprotein particles (snoRNPs) and that function in the processing and modification of pre-ribosomal RNAs.…”

Section: Discussionmentioning

confidence: 99%

“…It will be of great interest to determine whether this novel function identified for Pab2 is conserved in humans given the significant similarity between Pab2 and PABPN1. 47 Noteworthy is a recent study reporting the involvement of human PABPN1 in a viral-mediated polyadenylation-dependent RNA decay pathway, 51 possibly similar to the role of S. pombe Pab2 in polyadenylation-dependent RNA processing.…”

Section: Discussionmentioning

confidence: 99%

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Crossing the borders: Poly(A)-binding proteins working on both sides of the fence

Lemay

Lemieux²,

St-André³

et al. 2010

RNA Biology

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T he addition of a 3' poly(A) tail is a pre-requisite for the maturation of the majority of eukaryotic transcripts. In most eukaryotic species, RNA poly(A) tails are bound by two important poly(A)-binding proteins (PABPs): PABPC1 and PABPN1 that localize to the cytoplasm and the nucleus, respectively. Such steady state localization for PABPN1 and PABPC1 led to a model whereby PABPN1-bound nuclear mRNAs are remodeled during or after nuclear export so that PABPN1 is replaced by PABPC1 to allow robust cap-dependent translation in the cytoplasm. Here we discuss evidence that challenge the view in which PABPN1 and PABPC1 function solely in the nucleus and cytoplasm, respectively. We discuss accumulating evidence that support nuclear roles for PABPC1 in mRNA biogenesis as well as cytoplasmic roles for PABPN1 in translational control. Because 3' poly(A) tails can also act as a degradation mark via the exosome complex of 3'-5' exonucleases, we also discuss recent results that involve the nuclear PABP in posttranscriptional gene regulation.

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“…In the absence of methylation, the protein has an increased tendency to self-associate or aggregate (Perreault et al , 2007 ). This appears to be a more general phenomenon.…”

Section: Functional Consequences Of Pabpn1 Methylationmentioning

confidence: 99%

Methylation of the nuclear poly(A)-binding protein by type I protein arginine methyltransferases – how and why

Wahle

Moritz²

2013

Biological Chemistry

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Asymmetric dimethylation of arginine side chains in proteins is a frequent posttranslational modification, catalyzed by type I protein arginine methyltransferases (PRMTs). This article summarizes what is known about this modification in the nuclear poly(A)-binding protein (PABPN1). PABPN1 contains 13 dimethylated arginine residues in its C-terminal domain. Three enzymes, PRMT1, 3, and 6, can methylate PABPN1. Although 26 methyl groups are transferred to one PABPN1 molecule, the PRMTs do so in a distributive reaction, i.e., only a single methyl group is transferred per binding event. As PRMTs form dimers, with the active sites accessible from a small central cavity, backbone conformation around the methyl-accepting arginine is an important determinant of substrate specificity. Neither the association of PABPN1 with poly(A) nor its role in poly(A) tail synthesis is affected by arginine methylation. At least at low protein concentration, methylation does not affect the protein ' s tendency to oligomerize. The dimethylarginine residues of PABPN1 are located in the binding site for its nuclear import receptor, transportin. Arginine methylation weakens this interaction about 10-fold. Very recent evidence suggests that arginine methylation as a way of fine-tuning the interactions between transportin and its cargo may be a general mechanism.

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Regulation of the Nuclear Poly(A)-binding Protein by Arginine Methylation in Fission Yeast

Cited by 60 publications

References 78 publications

Negative Regulation of Meiotic Gene Expression by the Nuclear Poly(a)-binding Protein in Fission Yeast

Negative Regulation of Meiotic Gene Expression by the Nuclear Poly(a)-binding Protein in Fission Yeast

Crossing the borders: Poly(A)-binding proteins working on both sides of the fence

Methylation of the nuclear poly(A)-binding protein by type I protein arginine methyltransferases – how and why

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