Disease relevance of Slbp

• Hypomorphic dSLBP alleles support zygotic development but cause female sterility [1].
• Recombinant dSLBP expressed in insect cells by using the baculovirus system efficiently complements the depleted extract [2].

High impact information on Slbp

• Drosophila stem loop binding protein coordinates accumulation of mature histone mRNA with cell cycle progression [1].
• Eggs derived from females containing a viable, hypomorphic mutation in dSLBP store greatly reduced amounts of all five histone mRNAs in the egg, indicating that dSLBP is required in the maternal germ line for production of each histone mRNA [3].
• Developmental control of histone mRNA and dSLBP synthesis during Drosophila embryogenesis and the role of dSLBP in histone mRNA 3' end processing in vivo [3].
• Embryos deficient in zygotic dSLBP function accumulate poly(A)(+) versions of all five histone mRNAs as a result of usage of polyadenylation signals located 3' of the stem-loop in each histone gene [3].
• Cleavage of the Drosophila substrates is abolished by depleting the extract of the Drosophila stem-loop binding protein (dSLBP), indicating that both dSLBP and the stem-loop structure in histone pre-mRNA are essential components of the processing machinery [2].

Biological context of Slbp

• SLBP protein expression was examined during Drosophila development by using transgenes expressing hemagglutinin (HA) epitope-tagged proteins expressed from the endogenous Slbp promoter [4].
• A similar molecular phenotype also results from mutation of Slbp, which encodes the protein that binds the histone mRNA 3' stem-loop [5].
• U7 null mutants develop into sterile males and females, and these females display defects during oogenesis similar to germ line clones of Slbp null cells [5].
• Drosophila stem-loop binding protein intracellular localization is mediated by phosphorylation and is required for cell cycle-regulated histone mRNA expression [4].
• The N-terminal domain of the Drosophila histone mRNA binding protein, SLBP, is intrinsically disordered with nascent helical structure [6].

Associations of Slbp with chemical compounds

• Drosophila SLBP is phosphorylated at four out of five potential serine or threonine sites in the sequence DTAKDSNSDSDSD at the extreme C-terminus, and phosphorylation at these sites is necessary for histone pre-mRNA processing [7].

Other interactions of Slbp

• This may reflect a later onset of the histone pre-mRNA processing defect in U7 mutants compared to Slbp mutants, due to maternal stores of U7 snRNA [5].
• In vertebrates, the N-terminal domain of SLBP has sequence determinants necessary for histone mRNA translation, SLBP degradation, cyclin binding, and histone mRNA import [6].

Analytical, diagnostic and therapeutic context of Slbp

• We have used high-resolution NMR spectroscopy and circular dichroism to characterize the structural and dynamic features of this domain of SLBP from Drosophila (dSLBP) [6].

References