We investigated the influence of interferons a, 1, and y (IFN-a, -p, and -y) on the production of basic fibroblast growth factor (bFGF)

Metazoan replication-dependent histone mRNAs end in a conserved stem-loop rather than in the poly(A) tail found on all other mRNAs. The 3 end of histone mRNA binds a single class of proteins, the stem-loop binding proteins (SLBP). In Xenopus, there are two SLBPs: xSLBP1, the homologue of the mammalian SLBP, which is required for processing of histone pre-mRNA, and xSLBP2, which is expressed only during oogenesis and is bound to the stored histone mRNA in Xenopus oocytes. The stem-loop is required for efficient translation of histone mRNAs and substitutes for the poly(A) tail, which is required for efficient translation of other eucaryotic mRNAs. When a rabbit reticulocyte lysate is programmed with uncapped luciferase mRNA ending in the histone stem-loop, there is a three-to sixfold increase in translation in the presence of xSLBP1 while xSLBP2 has no effect on translation. Neither SLBP affected the translation of a luciferase mRNA ending in a mutant stem-loop that does not bind SLBP. Capped luciferase mRNAs ending in the stem-loop were injected into Xenopus oocytes after overexpression of either xSLBP1 or xSLBP2. Overexpression of xSLBP1 in the oocytes stimulated translation, while overexpression of xSLBP2 reduced translation of the luciferase mRNA ending in the histone stem-loop. A small region in the N-terminal portion of xSLBP1 is required to stimulate translation both in vivo and in vitro. An MS2-human SLBP1 fusion protein can activate translation of a reporter mRNA ending in an MS2 binding site, indicating that xSLBP1 only needs to be recruited to the 3 end of the mRNA but does not need to be directly bound to the histone stem-loop to activate translation.Replication-dependent histone mRNAs are unique among metazoan mRNAs because they are not polyadenylated but end, instead, in a highly conserved stem-loop (35). In contrast, histone mRNAs from fungi and plants are polyadenylated. Histone pre-mRNA processing requires only a single endonucleolytic cleavage to form the 3Ј end of the mature mRNA immediately after a highly conserved stem-loop structure (16). Most of the regulation of histone mRNA levels is mediated by the stem-loop and occurs at the posttranscriptional level, via regulation of mRNA processing and stability (22,44). It is likely that the stem-loop also fulfills the essential functions that are performed by the poly(A) tail on other mRNAs. One of these functions is to enhance the efficiency of translation (27,52). For example, the stem-loop has been shown to promote localization of histone mRNAs to polyribosomes (56). mRNAs ending in the histone stem-loop at the 3Ј end are translationally more active than messages ending in other stem-loops when transfected into Chinese hamster ovary cells (15).By using the yeast three-hybrid system, proteins that bind to the stem-loop have been isolated from several species (34,55,64,66). Although only a single SLBP is present in mammals (34, 66), Drosophila (55), and Caenorhabditis elegans, frog oocytes (46) express two SLBPs, called xSLBP1 and xSLBP2 (64). The ...

Translational repression by Drosophila Pumilio (Pum) protein controls posterior patterning during embryonic development. Here, we show that Pum is an important mediator of synaptic growth and plasticity at the neuromuscular junction (NMJ). Pum is localized to the postsynaptic side of the NMJ in third instar larvae and is also expressed in larval neurons. Neuronal Pum regulates synaptic growth. In its absence, NMJ boutons are larger and fewer in number, while Pum overexpression increases bouton number and decreases bouton size. Postsynaptic Pum negatively regulates expression of the translation factor eIF-4E at the NMJ, and Pum binds selectively to the 3'UTR of eIF-4E mRNA. The GluRIIa glutamate receptor is upregulated in pum mutants. These results, together with genetic epistasis studies, suggest that postsynaptic Pum modulates synaptic function via direct control of eIF-4E expression.