Association of the Mouse Infertility Factor DAZL1 with Actively Translating Polyribosomes1

Tsui, Shanli; Dai, Tiane; Warren, Stephen T.; Salido, Eduardo; Yen, Pauline H.

doi:10.1095/biolreprod62.6.1655

Cited by 73 publications

(70 citation statements)

References 37 publications

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“…(ii) Four of the proteins are encoded by loci shown genetically to be required for fertility in other organisms (PUM2, BOL, hQK3, and DAZL) (1,8,(17)(18)(19). (iii) Five of the proteins have been shown biochemically to interact with DAZ [BOL, DZIP1, DZIP2, hQK3 (data not shown)] and DAZL (14,20,21). These observations bolstered our confidence that we had identified legitimate partners.…”

Section: Identification Of Daz-interacting Proteinsmentioning

confidence: 69%

“…(i) Five of the candidate interacting proteins contain domains predicted to bind RNA (PUM2, BOL, DZIP1, DZIP2, and DAZL). DAZ homologs have also been shown to bind RNA and associate with ribosomes (14)(15)(16). This finding suggests that DAZ proteins may function with interacting proteins to regulate translation.…”

Section: Identification Of Daz-interacting Proteinsmentioning

confidence: 96%

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Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-Like proteins

Moore

Jaruzelska

Fox

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

208

215

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Early in development, a part of the embryo is set aside to become the germ cell lineage that will ultimately differentiate to form sperm and eggs and transmit genetic information to the next generation. Men with deletions encompassing the Y-chromosome DAZ genes have few or no germ cells but are otherwise healthy, indicating they harbor specific defects in formation or maintenance of germ cells. A DAZ homolog, DAZL (DAZ-Like), is found in diverse organisms, including humans and is required for germ cell development in males and͞or females. We identified proteins that interact with DAZ proteins to better understand their function in human germ cells. Here, we show that PUM2, a human homolog of Pumilio, a protein required to maintain germ line stem cells in Drosophila and Caenorhabditis elegans, forms a stable complex with DAZ through the same functional domain required for RNA binding, protein-protein interactions and rescue of Pumilio mutations in flies. We also show that PUM2 is expressed predominantly in human embryonic stem cells and germ cells and colocalizes with DAZ and DAZL in germ cells. These data implicate PUM2 as a component of conserved cellular machinery that may be required for germ cell development.A ll stem cells have potential to differentiate or proliferate mitotically. These potentials must be balanced for the stem cell population to be maintained. If differentiation exceeds proliferation, the stem cell population is not maintained. Evidence in humans suggests that the DAZ genes function early in the germ line stem cells. Men with deletions encompassing the Y-chromosome DAZ gene cluster have defects in spermatogenesis that are detected initially in the stem cell population. These men frequently lack all germ cells, including the spermatogonial stem cells, and only somatic cells are present in testicular tissue (1-3). In addition, expression of the DAZ gene and its ancestral, autosomal homolog, DAZL, only occurs in germ cells; DAZ is expressed in males, and DAZL is expressed in males and females (4, 5). Evidence from model organisms also suggests the DAZ genes function in germ cell maintenance. The Xenopus homolog of DAZ, Xdazl, is expressed in a region of the early oocyte that contains the germ plasm that is required for formation and maintenance of the germ cell lineage (6, 7). Inhibition of Xdazl leads to loss of the primordial germ cells (6, 7). Finally, the DAZ homolog in mice, Dazl, is most abundantly expressed in premeiotic germ cells; disruption of this gene causes depletion of germ cells beginning prenatally (8-10). DAZ and DAZL homologs may function interchangeably as suggested by the observation that a human DAZ transgene can partially rescue a mouse Dazl mutation (11). To shed light on how DAZ genes might function in human germ cells, we sought to identify proteins that interact with DAZ proteins. Materials and MethodsTwo-Hybrid Screening of DAZ-Interacting Proteins. The yeast two-hybrid system was used to identify proteins that interact with a DAZ:GAL4 DNA-binding domain fusion prot...

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Section: Identification Of Daz-interacting Proteinsmentioning

confidence: 69%

Section: Identification Of Daz-interacting Proteinsmentioning

confidence: 96%

Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-Like proteins

Moore

Jaruzelska

Fox

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

208

215

View full text Add to dashboard Cite

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“…The cytoplasmic localization of DAZ proteins, coupled with their ability to bind to RNA homopolymers through their RRM [22,23], infers a role for DAZL in post-transcriptional regulation. DAZL protein has been associated with actively translating polyribosomes, suggesting that it may mediate aspects of protein synthesis, including mRNA stability, transportation, localization, or translation [24,25]. DAZL is known to interact with poly(A)-binding proteins (PABPs) in vivo [26].…”

Section: Discussionmentioning

confidence: 99%

Deleted in Azoospermia-Like Enhances In Vitro Derived Porcine Germ Cell Formation and Meiosis

Park

Shen

Linher‐Melville

et al. 2013

Stem Cells and Development

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“…This family (DAZ, DAZ-like [DAZL], and BOULE) activates the translation of specific mRNAs in metazoan germ cells (Maegawa et al 2002;Collier et al 2005;Reynolds et al 2005Reynolds et al , 2007Brook et al 2009) via an interaction with the translation factor poly(A)-binding protein (PABP) . DAZAP1 interacts with the DAZ motif (Maegawa et al 2002), which is required both for the polysomal association of members of this family and for their ability to fully stimulate translation of reporter mRNAs (Tsui et al 2000b;Maegawa et al 2002;Collier et al 2005). Thus, DAZAP1 could contribute to DAZ-mediated translational activation.…”

Section: Introductionmentioning

confidence: 99%

DAZAP1, an RNA-binding protein required for development and spermatogenesis, can regulate mRNA translation

Smith¹,

Anderson²,

Smith³

et al. 2011

RNA

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DAZ-associated protein 1 (DAZAP1) is an RNA-binding protein required for normal growth, development, and fertility in mice. However, its molecular functions have not been elucidated. Here we find that Xenopus laevis and human DAZAP1, which are each expressed as short and long forms, act as mRNA-specific activators of translation in a manner that is sensitive to the number of binding sites present within the 39 UTR. Domain mapping suggests that this conserved function is mainly associated with C-terminal regions of DAZAP1. Interestingly, we find that the expression of xDAZAP1 and its polysome association are developmentally controlled, the latter suggesting that the translational activator function of DAZAP1 is regulated. However, ERK phosphorylation of DAZAP1, which can alter protein interactions with its C terminus, does not play a role in regulating its ability to participate in translational complexes. Since relatively few mRNA-specific activators have been identified, we explored the mechanism by which DAZAP1 activates translation. By utilizing reporter mRNAs with internal ribosome entry sites, we establish that DAZAP1 stimulates translation initiation. Importantly, this activity is not dependent on the recognition of the 59 cap by initiation factors, showing that it functions downstream from this frequently regulated event, but is modulated by changes in the adenylation status of mRNAs. This suggests a function in the formation of ''end-to-end'' complexes, which are important for efficient initiation, which we show to be independent of a direct interaction with the bridging protein eIF4G.

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Association of the Mouse Infertility Factor DAZL1 with Actively Translating Polyribosomes1

Cited by 73 publications

References 37 publications

Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-Like proteins

Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-Like proteins

Deleted in Azoospermia-Like Enhances In Vitro Derived Porcine Germ Cell Formation and Meiosis

DAZAP1, an RNA-binding protein required for development and spermatogenesis, can regulate mRNA translation

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