Disease relevance of SLBP

• Using hairpin II of U1 small nuclear RNA (U1hpII) or the 3' stem loop of histone mRNA as bait, we could selectively amplify T7 phage that display either the spliceosomal protein U1A or the histone stem loop-binding protein from a lung cDNA phage library containing more than 10(7) independent clones [1].
• Analysis of tissue biopsies from patients with necrotizing fasciitis revealed recruitment of neutrophils and monocytes to the infectious site, combined with the release of HBP [2].
• The results show that M protein, in synergy with HBP, evokes an inflammatory response that may contribute to the profound pathophysiological consequences seen in severe streptococcal infections [2].
• We hypothesized a stepwise increase in these platelet activation indices between healthy controls (HC, n = 60), 'high-risk' essential hypertensive subjects (HBP, n = 45) and treated, previously diagnosed patients with malignant phase hypertension (MHT, n = 45) [3].
• No HBP has been described in Brucella spp [4].

High impact information on SLBP

• The stem-loop binding protein (SLBP) is the posttranscriptional regulator of histone mRNA in metazoan cells [5].
• SLBP binds histone pre-mRNAs and facilitates 3'-end processing by promoting stable association of U7 snRNP with the pre-mRNA [5].
• Translation of the HBP open reading frame in vitro produced a 43 kDa protein with RNA binding specificity identical to murine or bovine HBP [6].
• The HBP gene is composed of eight exons covering 19.5 kb on the short arm of chromosome 4 [6].
• Drosophilia SLBP is heavily phosphorylated, containing up to seven phosphoryl groups [7].

Biological context of SLBP

• SLBP is also regulated during the cell cycle, accumulating as cells enter S phase and being rapidly degraded as cells exit S phase [8].
• Mutation of any residues in a TTP sequence (amino acids 60 to 62) or mutation of a consensus cyclin binding site (amino acids 99 to 104) stabilizes SLBP in G2 and mitosis [8].
• Cells that express a stable SLBP still degrade histone mRNA at the end of S phase, demonstrating that degradation of SLBP is not required for histone mRNA degradation [8].
• Phosphorylation of stem-loop binding protein (SLBP) on two threonines triggers degradation of SLBP, the sole cell cycle-regulated factor required for regulation of histone mRNA processing, at the end of S phase [8].
• Thus, only the Impalpha/Impbeta pathway contributes to SLBP nuclear import in HeLa cells [9].

Anatomical context of SLBP

• T230 is highly conserved; we have determined that this site is also completely phosphorylated in baculovirus-expressed mammalian SLBP and extensively phosphorylated in both Drosophila and mammalian cultured cells [7].
• 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 [10].
• Only 5-10% of the SLBP could be extracted from the polyribosomes with salt [11].
• In the nucleus, both U7 snRNP and SLBP are present in coiled bodies, structures that are associated with histone genes and may play a direct role in histone pre-mRNA processing in vivo [12].
• Heparin-binding proteins (HBP) from seminal plasma have been expected to participate in modulation of the acrosomal reaction, and have been correlated with fertility in some species [13].

Associations of SLBP with chemical compounds

• On the other hand, the tendency for the anaerobic biodegradability was; BPF > HBP > BPS, BPA, TDP > BPE > BPB [14].

Physical interactions of SLBP

• The cleavage of histone pre-mRNA to form the unique 3' end requires the U7 snRNP and the stem-loop binding protein (SLBP) that binds the 3' end of histone mRNA [15].

Regulatory relationships of SLBP

• Removal of SLBP by RNA interference causes an increase in the number of cells in S-phase and this effect can be reversed by expressing an exogenous SLBP resistant to the small interfering RNA [16].
• These data indicate that SLBP stimulates the translation of histone mRNAs through a functional interaction with both the mRNA stem-loop and the 5' cap that is mediated by eIF4G and eIF3 [17].

Other interactions of SLBP

• It is likely that the RBD of SLBP interacts directly with both the stem-loop RNA and other processing factor(s), most likely the U7 snRNP, to facilitate histone pre-mRNA processing [18].
• We previously identified a 100-kDa zinc finger protein (ZFP100) as a component of U7 snRNP that interacts with the SLBP/pre-mRNA complex [19].

Analytical, diagnostic and therapeutic context of SLBP

• To identify other factors involved in histone pre-mRNA processing, we used a modified yeast two-hybrid assay in which SLBP and its RNA target were coexpressed as bait [5].
• We also analyze the messages bound to the endogenous SLBP on polyribosomes by immunoprecipitation [20].
• Electrophoretic mobility shift assays demonstrated that the SLBP-induced opening of HDE actually facilitates U7 snRNA anchoring on the histone H4-12 pre-mRNAs 3' end [21].
• OBJECTIVES: (1) To compare blood pressure (BP) readings with an automated arm cuff oscillometric device (AutoBP) to readings with a mercury sphygmomanometer (HgBP) and (2) to evaluate the impact on the prevalence of hypertension (HBP) in a population-based survey [22].

References