NCBI Summary:
This gene encodes a member of the PUF family, evolutionarily conserved RNA-binding proteins related to the Pumilio proteins of Drosophila and the fem-3 mRNA binding factor proteins of C. elegans. The encoded protein contains a sequence-specific RNA binding domain comprised of eight repeats and N- and C-terminal flanking regions, and serves as a translational regulator of specific mRNAs by binding to their 3' untranslated regions. The evolutionarily conserved function of the encoded protein in invertebrates and lower vertebrates suggests that the human protein may be involved in translational regulation of embryogenesis, and cell development and differentiation. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
General function
Cell proliferation
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Cellular localization
Nuclear
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Ovarian function
Germ cell development, Oogenesis, Oocyte maturation, Early embryo development
Comment
A role of Pumilio 1 in mammalian oocyte maturation and maternal phase of embryogenesis. Mak W et al. (2018) RNA binding proteins play a pivotal role during the oocyte-to-embryo transition and maternal phase of embryogenesis in invertebrates, but their function in these processes in mammalian systems remain largely understudied. Here we report that a member of the Pumilio/FBF family of RNA binding proteins in mice, Pumilio 1 (Pum1), is a maternal effect gene. The absence of maternal PUM1 in the oocyte does not affect meiotic maturation but leads to abnormal preimplantation development. Furthermore, genome-wide transcriptome analysis of oocytes and embryos revealed that there is a concomitant perturbation of the mRNA milieu. Of note, putative PUM1 mRNA targets were equally perturbed as non-direct targets, which indicates that PUM1 regulates the stability of maternal mRNAs both directly and indirectly. We show Cdk1 mRNA, a known PUM1 target essential for meiosis and preimplantation development, is not degraded appropriately during meiosis, leading to an increase in CDK1 protein in mature oocytes, which indicates that PUM1 post-transcriptionally regulates Cdk1 mRNA; this could partially explain the observed abnormal preimplantation development. Furthermore, our results show that maternal and zygotic PUM1 are required for postnatal survival. These findings indicate that PUM1 is essential in the process of cytoplasmic maturation and developmental competence of the oocyte. These results reveal an important function of maternal PUM1 as a post-transcriptional regulator during mammalian embryogenesis.//////////////////
An Important Role of Pumilio 1 in Regulating the Development of the Mammalian Female Germline. Mak W et al. (2016) PUF (Pumilio/FBF) proteins are a highly conserved family of translational regulators. The Drosophila PUF protein, Pumilio is crucial for germline establishment and fertility. In mammals, primordial folliculogenesis is a key process that establishes the initial cohort of female mammalian germ cells prior to birth and this primordial follicle pool is a prerequisite for female reproductive competence. We sought to understand whether PUF proteins have a conserved role in mammals during primordial folliculogenesis and female reproductive competency. In mammals, two homologs of Pumilio exist: Pumilio 1 and Pumilio 2. Here we report that PUMILIO1 (PUM1) plays an important role in the establishment of the primordial follicle pool, meiosis, and female reproductive competency, whereas PUMILIO2 (PUM2) does not play a detectable function in these processes. Furthermore, we show that PUM1 facilitates the transition of the late meiotic prophase I oocyte from pachytene to diplotene stage by regulating SYCP1 protein. Our study reveals an important role of translational regulation in mammalian female germ cell development.//////////////////
Johnson et al reported germline stem cells and follicular renewal in the postnatal mammalian ovary. Pumilio-1 was found to be expressed in the ovary.
Expression regulated by
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Ovarian localization
Primordial Germ Cell, Oocyte
Comment
Changes in subcellular structures and states of Pumilio1 regulate the translation of target Mad2 and Cyclin B1 mRNAs. Takei N et al. (2020) Temporal and spatial control of mRNA translation has emerged as a major mechanism for promoting diverse biological processes. However, the molecular nature of temporal and spatial control of translation remains unclear. In oocytes, many mRNAs are deposited as a translationally repressed form and are translated at appropriate timings to promote the progression of meiosis and development. Here, we show that changes in subcellular structures and states of the RNA-binding protein Pumilio1 regulate the translation of target mRNAs and progression of oocyte maturation. Pumilio1 was shown to bind to Mad2 and Cyclin B1 mRNAs, assemble highly clustered aggregates, and surround Mad2 and Cyclin B1 RNA granules in mouse oocytes. These Pumilio1 aggregates were dissolved prior to the translational activation of target mRNAs possibly by phosphorylation. Stabilization of Pumilio1 aggregates prevented the translational activation of target mRNAs and progression of oocyte maturation. Together, our results provide an aggregation-dissolution model for the temporal and spatial control of translation.//////////////////
Follicle stages
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Phenotypes
Mutations
2 mutations
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Variation analysis of PUM1 gene in Chinese women with primary ovarian insufficiency. Luo W et al. (2018) Accumulating evidence has indicated that the genes involved in meiosis are highly correlated with ovarian function. Pumilio 1 (PUM1) is a RNA-binding protein which is involved in the meiotic process. It has been reported that the Pum1 knockout female mice displayed subfertility due to the decrease in primordial follicle pool. The aim of our study is to investigate whether variants of the PUM1 gene are responsible for primary ovarian insufficiency (POI) in Chinese women. We analyzed coding sequence and untranslated regions of the PUM1 gene in 196 Han Chinese women with non-syndromic POI and 192 controls. Seven novel variants were identified, but one of them was synonymous and six were intronic. Besides, seven known single-nucleotide polymorphisms (SNPs) were found, and there were no significant differences in genotype and allele frequencies of the SNPs between patients and controls. The results suggest that the variants in PUM1 may not contribute to POI in Han Chinese women.//////////////////
Species: mouse
Mutation name: type: null mutation fertility: subfertile Comment: Pumilio1 haploinsufficiency leads to SCA1-like neurodegeneration by increasing wild-type Ataxin1 levels. Gennarino VA et al. (2015) Spinocerebellar ataxia type 1 (SCA1) is a paradigmatic neurodegenerative proteinopathy, in which a mutant protein (in this case, ATAXIN1) accumulates in neurons and exerts toxicity; in SCA1, this process causes progressive deterioration of motor coordination. Seeking to understand how post-translational modification of ATAXIN1 levels influences disease, we discovered that the RNA-binding protein PUMILIO1 (PUM1) not only directly regulates ATAXIN1 but also plays an unexpectedly important role in neuronal function. Loss of Pum1 caused progressive motor dysfunction and SCA1-like neurodegeneration with motor impairment, primarily by increasing Ataxin1 levels. Breeding Pum1(+/-) mice to SCA1 mice (Atxn1(154Q/+)) exacerbated disease progression, whereas breeding them to Atxn1(+/-) mice normalized Ataxin1 levels and largely rescued the Pum1(+/-) phenotype. Thus, both increased wild-type ATAXIN1 levels and PUM1 haploinsufficiency could contribute to human neurodegeneration. These results demonstrate the importance of studying post-transcriptional regulation of disease-driving proteins to reveal factors underlying neurodegenerative disease.//////////////////