NCBI Summary:
This gene encodes a protein that binds to the stem-loop structure in replication-dependent histone mRNAs. Histone mRNAs do not contain introns or polyadenylation signals, and are processed by endonucleolytic cleavage. The stem-loop structure is essential for efficient processing but this structure also controls the transport, translation and stability of histone mRNAs. Expression of the protein is regulated during the cell cycle, increasing more than 10-fold during the latter part of G1. [provided by RefSeq, Jul 2008]
The stem-loop binding protein regulates translation of histone mRNA during mammalian oogenesis Allard P, et al .
Although messenger RNAs encoding the histone proteins are among the most abundant in mammalian oocytes, the mechanism regulating their translation has not been identified. The stem-loop binding protein (SLBP) binds to a highly conserved sequence in the 3'-untranslated region (utr) of the non-polyadenylated histone mRNAs in somatic cells and mediates their stabilization and translation. We previously showed that SLBP, which is expressed only during S-phase of proliferating cells, is expressed in growing oocytes at G2 of the cell cycle and accumulates substantially during meiotic maturation. We report here that elevating the amount of SLBP in immature (G2) oocytes is sufficient to increase translation of a reporter mRNA bearing the histone 3'-utr and endogenous histone synthesis and that this effect is not mediated through increased stability of the encoding mRNAs. We further report that translation of the reporter mRNA increases dramatically during meiotic maturation coincident with the accumulation of SLBP. Conversely, when SLBP accumulation during maturation is prevented using RNA interference, both translation of the reporter mRNA and synthesis of endogenous histones are significantly reduced. This effect is not mediated by a loss of the encoding mRNAs. Moreover, following fertilization, SLBP-depleted oocytes also show a significant decrease in pronuclear size and in the amount of acetylated histone detectable on the chromatin. These results demonstrate that histone synthesis in immature and maturing oocytes is governed by a translational control mechanism that is directly regulated by changes in the amount of SLBP.
Follicle stages
Antral, Preovulatory
Comment
Allegro: Analyzing expression and sequence in concert to discover regulatory programs. Halperin Y et al. A major goal of system biology is the characterization of transcription factors and microRNAs (miRNAs) and the transcriptional programs they regulate. We present Allegro, a method for de-novo discovery of cis-regulatory transcriptional programs through joint analysis of genome-wide expression data and promoter or 3' UTR sequences. The algorithm uses a novel log-likelihood-based, non-parametric model to describe the expression pattern shared by a group of co-regulated genes. We show that Allegro is more accurate and sensitive than existing techniques, and can simultaneously analyze multiple expression datasets with more than 100 conditions. We apply Allegro on datasets from several species and report on the transcriptional modules it uncovers. Our analysis reveals a novel motif over-represented in the promoters of genes highly expressed in murine oocytes. The present gene id highly expressed in the oocyte and has a unique promoter motif.
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: infertile - ovarian defect Comment: Stem-loop binding protein expressed in growing oocytes is required for accumulation of mRNAs encoding histones H3 and H4 and for early embryonic development in the mouse. Arnold DR et al. Growing oocytes accumulate mRNAs and proteins that support early embryogenesis. Among the most abundant of these maternal factors are the histones. Histone mRNA accumulation and translation are mainly restricted to S-phase in somatic cells, and the mechanism by which oocytes produce histones is unknown. In somatic cells, replication-dependent histone synthesis requires the stem-loop binding protein (SLBP). SLBP is expressed during S-phase, binds to the 3'-untranslated region of non-polyadenylated transcripts encoding the histones, and is required for their stabilization and translation. SLBP is expressed in oocytes of several species, suggesting a role in histone synthesis. To test this, we generated transgenic mice whose oocytes lack SLBP. mRNAs encoding histones H3 and H4 failed to accumulate in these oocytes. Unexpectedly, mRNAs encoding H2A and H2B were little affected. Embryos derived from SLBP-depleted oocytes reached the 2-cell stage, but most then became arrested. Histones H3 and H4, but not H2A or H2B, were substantially reduced in these embryos. The embryos also expressed high levels of gammaH2A.X. Injection of histones into SLBP-depleted embryos rescued them from developmental arrest. Thus, SLBP is an essential component of the mechanism by which growing oocytes of the mouse accumulate the histones that support early embryonic development.