Identification of Target Messenger RNA Substrates for the Murine Deleted in Azoospermia-Like RNA-Binding Protein1

Jiao, Xuan; Trifillis, Panayiota; Kiledjian, Megerditch

doi:10.1095/biolreprod66.2.475

Cited by 94 publications

(87 citation statements)

References 74 publications

(118 reference statements)

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“…While DAZ and DAZL contain RNA recognition motifs (RRMs), a consensus binding sequence has not been clearly delineated. For example, a G/CU-rich sequence is important for the binding of DAZL to some target RNAs, while a U-rich sequence appears to be important for others (Jiao et al 2002;Fox et al 2005). Perhaps a DAZ/DAZL-binding specificity is modulated by interacting factors that differ among cell types.…”

Section: Discussionmentioning

confidence: 99%

Regulated Pumilio-2 binding controls RINGO/Spy mRNA translation and CPEB activation

Padmanabhan¹,

Richter²

2006

Genes Dev.

125

174

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CPEB is a sequence-specific RNA-binding protein that controls the polyadenylation-induced translation of mos and cyclin B1 mRNAs in maturing Xenopus oocytes. CPEB activity requires not only the phosphorylation of S174, but also the synthesis of a heretofore-unknown upstream effector molecule. We show that the synthesis of RINGO/Spy, an atypical activator of cyclin-dependent kinases (cdks), is necessary for CPEB-directed polyadenylation. Deletion analysis and mRNA reporter assays show that a cis element in the RINGO/Spy 3 UTR is necessary for translational repression in immature (G2-arrested) oocytes. The repression is mediated by 3 UTR Pumilio-Binding Elements (PBEs), and by its binding protein Pumilio 2 (Pum2). Pum2 also interacts with the Xenopus homolog of human Deleted for Azoospermia-like (DAZL) and the embryonic poly(A)-binding protein (ePAB). Following the induction of maturation, Pum2 dissociates not only from RINGO/Spy mRNA, but from XDAZL and ePAB as well; as a consequence, RINGO/Spy mRNA is translated. These results demonstrate that a reversible Pum2 interaction controls RINGO/Spy mRNA translation and, as a result, CPEB-mediated cytoplasmic polyadenylation.

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Section: Discussionmentioning

confidence: 99%

Regulated Pumilio-2 binding controls RINGO/Spy mRNA translation and CPEB activation

Padmanabhan¹,

Richter²

2006

Genes Dev.

125

174

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“…(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: 95%

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.

207

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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“…Efforts to identify in vivo mRNA targets of mammalian DAZL family proteins utilized varied approaches but have been mainly restricted to mDAZL (reviewed in ) and have identified multiple putative targets (Jiao et al 2002, 2007. These studies focused on testis-expressed mRNAs but it is likely that at least a subset of the identified mRNAs are regulated during oogenesis.…”

Section: Mrna Targets Of Dazl Family Protein-mediated Regulation Of Tmentioning

confidence: 99%

The DAZL and PABP families: RNA-binding proteins with interrelated roles in translational control in oocytes

Brook¹,

Smith²,

Gray³

2009

Reproduction

107

114

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Gametogenesis is a highly complex process that requires the exquisite temporal, spatial and amplitudinal regulation of gene expression at multiple levels. Translational regulation is important in a wide variety of cell types but may be even more prevalent in germ cells, where periods of transcriptional quiescence necessitate the use of post-transcriptional mechanisms to effect changes in gene expression. Consistent with this, studies in multiple animal models have revealed an essential role for mRNA translation in the establishment and maintenance of reproductive competence. While studies in humans are less advanced, emerging evidence suggests that translational regulation plays a similarly important role in human germ cells and fertility. This review highlights specific mechanisms of translational regulation that play critical roles in oogenesis by activating subsets of mRNAs. These mRNAs are activated in a strictly determined temporal manner via elements located within their 3 0 UTR, which serve as binding sites for trans-acting factors. While we concentrate on oogenesis, these regulatory events also play important roles during spermatogenesis. In particular, we focus on the deleted in azoospermia-like (DAZL) family of proteins, recently implicated in the translational control of specific mRNAs in germ cells; their relationship with the general translation initiation factor poly(A)-binding protein (PABP) and the process of cytoplasmic mRNA polyadenylation.

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Identification of Target Messenger RNA Substrates for the Murine Deleted in Azoospermia-Like RNA-Binding Protein1

Cited by 94 publications

References 74 publications

Regulated Pumilio-2 binding controls RINGO/Spy mRNA translation and CPEB activation

Regulated Pumilio-2 binding controls RINGO/Spy mRNA translation and CPEB activation

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

The DAZL and PABP families: RNA-binding proteins with interrelated roles in translational control in oocytes

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