Wdr12, a Mouse Gene Encoding a Novel WD-Repeat Protein with a Notchless-like Amino-terminal Domain

Nal, Béatrice; Mohr, Elodie; Silva, Maria-Isabel Da; Tagett, Rebecca; Navarro, Christel; Carroll, Patrick; Depetris, Danielle; Verthuy, Christophe; Jordan, Bertrand; Ferrier, Pierre

doi:10.1006/geno.2001.6682

Cited by 29 publications

(31 citation statements)

References 40 publications

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“…To determine which portion of Ytm1 is responsible for this interaction, we assayed binding in vitro to GST-Erb1 of the N-terminal 98 amino acids of Ytm1 (Ytm1-N) containing the Notchless-like element (Nal et al, 2002), and the C-terminal 362 amino acids of Ytm1 (Ytm1-C) containing seven WD40 repeats (Miles et al, 2005; Figure 2A). Although the function of the Notchless-like element is unknown (see Discussion), the WD40 repeats form a beta-propeller structure, a well-characterized proteinprotein interaction domain (reviewed in Smith et al, 1999).…”

Section: Ytm1 Binds Erb1 Via Its C-terminal Wd40 Repeatsmentioning

confidence: 99%

“…This sequence was originally identified in the N-terminal part of Notchless, a protein implicated in the modulation of Notch signaling in Drosophila (Royet et al, 1998). Previously, Nal et al (2002) found a direct interaction between GST-WDR12 and the intracytoplasmic domain of the Notch1 protein in vitro, presumably via the Nle of WDR12. Because there are no known Notch homologues in yeast, the function of the Nle in Ytm1 remains unclear.…”

Section: Roles For Domains Other Than Interactions Within the Nop7-sumentioning

confidence: 99%

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Interactions among Ytm1, Erb1, and Nop7 Required for Assembly of the Nop7-Subcomplex in Yeast Preribosomes

Tang

Sahasranaman

Jakovljevic

et al. 2008

MBoC

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In Saccharomyces cerevisiae, more than 180 assembly factors associate with preribosomes to enable folding of pre-rRNA, recruitment of ribosomal proteins, and processing of pre-rRNAs to produce mature ribosomes. To examine the molecular architecture of preribosomes and to connect this structure to functions of each assembly factor, assembly subcomplexes have been purified from preribosomal particles. The Nop7-subcomplex contains three assembly factors: Nop7, Erb1, and Ytm1, each of which is necessary for conversion of 27SA 3 pre-rRNA to 27SB S pre-rRNA. However, interactions among these three proteins and mechanisms of their recruitment and function in pre-rRNPs are poorly understood. Here we show that Ytm1, Erb1, and Nop7 assemble into preribosomes in an interdependent manner. We identified which domains within Ytm1, Erb1, and Nop7 are necessary for their interaction with each other and are sufficient for recruitment of each protein into preribosomes. Dominant negative effects on growth and ribosome biogenesis caused by overexpressing truncated Ytm1, Erb1, or Nop7 constructs, and recessive phenotypes of the truncated proteins revealed not only interaction domains but also other domains potentially important for each protein to function in ribosome biogenesis. Our data suggest a model for the architecture of the Nop7-subcomplex and provide potential functions of domains of each protein.

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Section: Ytm1 Binds Erb1 Via Its C-terminal Wd40 Repeatsmentioning

confidence: 99%

Section: Roles For Domains Other Than Interactions Within the Nop7-sumentioning

confidence: 99%

Interactions among Ytm1, Erb1, and Nop7 Required for Assembly of the Nop7-Subcomplex in Yeast Preribosomes

Tang

Sahasranaman

Jakovljevic

et al. 2008

MBoC

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“…Bioinformatic analysis revealed that the N-terminal UBL domain of Rsa4 is homologous to the N-terminal UBL domain of Ytm1, suggesting that Rea1 could interact with Ytm1 through its MIDAS domain (21). Earlier work in mice also suggested that the N-terminal domain of WDR12 showed similarity to the N-terminal domain of Nle1, and it was originally referred to in the literature as the Nle1 domain (26). Subsequent experiments in S. cerevisiae demonstrated that Ytm1 interacts with Rea1 through its UBL domain.…”

mentioning

confidence: 99%

The Crystal Structure of the Ubiquitin-like Domain of Ribosome Assembly Factor Ytm1 and Characterization of Its Interaction with the AAA-ATPase Midasin

Romes

Sobhany

Stanley

2016

Journal of Biological Chemistry

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The synthesis of eukaryotic ribosomes is a complex, energetically demanding process requiring the aid of numerous nonribosomal factors, such as the PeBoW complex. The mammalian PeBoW complex, composed of Pes1, Bop1, and WDR12, is essential for the processing of the 32S preribosomal RNA. Previous work in Saccharomyces cerevisiae has shown that release of the homologous proteins in this complex (Nop7, Erb1, and Ytm1, respectively) from preribosomal particles requires Rea1 (midasin or MDN1 in humans), a large dynein-like protein.Midasin contains a C-terminal metal ion-dependent adhesion site (MIDAS) domain that interacts with the N-terminal ubiquitin-like (UBL) domain of Ytm1/WDR12 as well as the UBL domain of Rsa4/Nle1 in a later step in the ribosome maturation pathway. Here we present the crystal structure of the UBL domain of the WDR12 homologue from S. cerevisiae at 1.7 Å resolution and demonstrate that human midasin binds to WDR12 as well as Nle1 through their respective UBL domains. Midasin contains a well conserved extension region upstream of the MIDAS domain required for binding WDR12 and Nle1, and the interaction is dependent upon metal ion coordination because removal of the metal or mutation of residues that coordinate the metal ion diminishes the interaction. Mammalian WDR12 displays prominent nucleolar localization that is dependent upon active ribosomal RNA transcription. Based upon these results, we propose that release of the PeBoW complex and subsequent release of Nle1 by midasin is a well conserved step in the ribosome maturation pathway in both yeast and mammalian cells.Ribosomes are large macromolecular machines composed of four pieces of ribosomal RNA (rRNA) 2 and 80 (79 in yeast) associated ribosomal proteins (1, 2). Ribosomes are responsible for carrying out the synthesis of all proteins within a cell, and the eukaryotic ribosome is composed of two subunits known as the small subunit (40S) and the large subunit (60S). The assembly of ribosomes begins in the nucleolus with the transcription of the rRNAs. Three of the rRNAs are transcribed as a single polycistronic precursor (18S, 5.8S, and 25S), which must then be modified, folded, processed, and exported to the cytoplasm in a carefully orchestrated manner (3, 4). Ribosome biogenesis in eukaryotic cells is an incredibly complex and energetically demanding process that requires more than 200 essential nonribosomal assembly factors (3-6). Defects in the mammalian ribosome biogenesis pathway are linked to a group of human diseases that are collectively called ribosomopathies. These are all congenital, inherited disorders with a broad clinical spectrum that have perplexed researchers for years because they cause tissue-specific effects although ribosomes are essential in all cell types (7). Ribosome biogenesis has also been emerging as a new target for cancer therapy. Recent studies have shown that several important oncogenes, including cMYC, RAS, and PI3K, play key roles in promoting hyperactive ribosome biogenesis, and deregulated ribosomal DNA...

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“…Members of this family interact with several protein partners and are involved in many cellular functions (40). An Nle-like amino-terminal domain was also found in another protein, named Wdr12, recently identified during a genetic screen for modulators of T-lymphocyte differentiation (29). The nuclear Wdr12 protein is composed of seven WD40 repeat domains, which, however, are not related to the WD40 domains of mouse Nle (mNle).…”

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confidence: 99%

The Murine Ortholog of Notchless, a Direct Regulator of the Notch Pathway in Drosophila melanogaster, Is Essential for Survival of Inner Cell Mass Cells

Cormier

Bras

Souilhol

et al. 2006

Molecular and Cellular Biology

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Notch signaling is an evolutionarily conserved pathway involved in intercellular communication and is essential for proper cell fate choices. Numerous genes participate in the modulation of the Notch signaling pathway activity. Among them, Notchless (Nle) is a direct regulator of the Notch activity identified in Drosophila melanogaster. Here, we characterized the murine ortholog of Nle and demonstrated that it has conserved the ability to modulate Notch signaling. We also generated mice deficient for mouse Nle (mNle) and showed that its disruption resulted in embryonic lethality shortly after implantation. In late mNle ؊/؊ blastocysts, inner cell mass (ICM) cells died through a caspase 3-dependent apoptotic process. Most deficient embryos exhibited a delay in the temporal down-regulation of Oct4 expression in the trophectoderm (TE). However, mNle-deficient TE was able to induce decidual swelling in vivo and properly differentiated in vitro. Hence, our results indicate that mNle is mainly required in ICM cells, being instrumental for their survival, and raise the possibility that the death of mNle-deficient embryos might result from abnormal Notch signaling during the first steps of development.

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Wdr12, a Mouse Gene Encoding a Novel WD-Repeat Protein with a Notchless-like Amino-terminal Domain

Cited by 29 publications

References 40 publications

Interactions among Ytm1, Erb1, and Nop7 Required for Assembly of the Nop7-Subcomplex in Yeast Preribosomes

Interactions among Ytm1, Erb1, and Nop7 Required for Assembly of the Nop7-Subcomplex in Yeast Preribosomes

The Crystal Structure of the Ubiquitin-like Domain of Ribosome Assembly Factor Ytm1 and Characterization of Its Interaction with the AAA-ATPase Midasin

The Murine Ortholog of Notchless, a Direct Regulator of the Notch Pathway in Drosophila melanogaster, Is Essential for Survival of Inner Cell Mass Cells

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