Disease relevance of pum

• First, ovary-specific expression of pum partially rescues bem female sterility [1].
• Transmission electron microscopy (TEM) revealed no virions in pre-vitellogenic or vitellogenic ova, or in the lateral oviduct of D. longicaudata females [2].
• In mice, cloned genes or retroviruses can be inserted by manipulation of newly fertilized ova, and intensive research is aimed at understanding the basis for regulation of gene expression using this technique [3].

High impact information on pum

• These and other observations suggest that pum acts by recognizing the NRE and then recruiting nos [4].
• Binding of pumilio to maternal hunchback mRNA is required for posterior patterning in Drosophila embryos [4].
• Pumilio controls germline stem cells in Drosophila females, and, in lower eukaryotes, PUF proteins promote continued mitoses [5].
• The Drosophila gene pumilio is expressed maternally, and its function is essential during early embryogenesis for the formation of abdominal segments [6].
• Puf proteins regulate translation and mRNA stability by binding sequences in their target RNAs through the Pumilio homology domain (PUM-HD), which is characterized by eight tandem copies of a 36 amino acid motif, the PUM repeat [7].

Biological context of pum

• Analogous to their function in body patterning, nos and pum require each other to control dendrite morphogenesis, a process likely to involve translational regulation of nos itself [8].
• Given the coordinate function of nanos and pumilio in embryonic patterning, we analyzed the role of these genes in oogenesis [9].
• Although the nanos and pumilio ovarian phenotypes have similarities and both genes ultimately affect germline stem cell development, the focus of these phenotypes appears to be different [9].
• The control of dendrite morphogenesis by Nos/Pum, however, does not require hunchback, which is essential for body patterning [8].
• Finally, pum mutation causes premature mitosis in the migrating pole cells [10].

Anatomical context of pum

• Nanos and Pumilio have critical roles in the development and function of Drosophila germline stem cells [9].
• First, a mutation in pum causes a defect in pole-cell migration into the gonads [10].
• We also show that Nos and Pum can repress cap-independent translation from an internal ribosome entry site (IRES) in vivo, suggesting that they act downstream of the initial steps of normal, cap-dependent translation [11].
• Here, we show that Pum is an important mediator of synaptic growth and plasticity at the neuromuscular junction (NMJ) [12].
• These studies demonstrate that evolutionarily distant organisms utilize conserved factors to regulate early germ cell development and survival, and that these factors include members of the nanos and pumilio gene families [13].

Associations of pum with chemical compounds

• The GluRIIa glutamate receptor is upregulated in pum mutants [12].
• The pum cDNA encodes a 157 x 10(3) M(r) protein which consists mainly of regions enriched in a single amino acid, usually glycine, alanine, glutamine or serine/threonine [14].

Physical interactions of pum

• In this report we use protein-protein and protein-RNA interaction assays in yeast and in vitro to show that Nanos forms a ternary complex with the RNA-binding domain of Pumilio and the NRE [15].
• The PUMILIO (PUM) protein is thought to bind the NREs and thereby repress hb translation [16].

Regulatory relationships of pum

• These data demonstrate that the poly(A) tail is not required for regulation and suggest that NOS and PUM can regulate hb translation by two mechanisms: removal of the poly(A) tail and a poly(A)-independent pathway that directly affects translation [17].
• We demonstrate that the prototypical Puf protein Pumilio temporally regulates bicoid (bcd) mRNA translation via evolutionarily conserved Nanos response elements (NRE) in its 3'UTR [18].
• We show that Pum inhibits pole-cell division by repressing translation of cyclin B messenger RNA [10].
• The translational repressor Pumilio regulates presynaptic morphology and controls postsynaptic accumulation of translation factor eIF-4E [12].
• Maternal Nanos and Pumilio regulate zygotic vasa expression autonomously in the germ-line progenitors of Drosophila melanogaster embryos [19].

Other interactions of pum

• While pumilio mutant ovaries fail to maintain stem cells and all germline cells differentiate into egg chambers, the focus of nanos function seems to lie in the differentiation of the stem cell progeny, the cystoblast [9].
• Phenotypically, embryos from transgenic mothers that harbor bcd NRE mutations exhibited dominant anterior patterning defects and we discovered similar head defects in embryos from pum(-) mothers [18].
• Regulatory relationship among piwi, pumilio, and bag-of-marbles in Drosophila germline stem cell self-renewal and differentiation [20].
• These results, together with genetic epistasis studies, suggest that postsynaptic Pum modulates synaptic function via direct control of eIF-4E expression [12].
• In cystoblasts, accumulating Bam protein antagonizes pumilio, permitting the translation of cystoblast-promoting transcripts [21].

Analytical, diagnostic and therapeutic context of pum

• We generated transgenic flies expressing affinity-tagged PUMILIO under the control of an ovary-specific promoter, and we purified PUMILIO from whole adult flies and embryos and analyzed associated mRNAs by using DNA microarrays [22].

References