A region of Drosophila SLBP distinct from the histone pre-mRNA binding and processing domains is essential for deposition of histone mRNA in the oocyte

Abstract

During Drosophila oogenesis, large amounts of histone mRNA and proteins are deposited in the developing oocyte. These are sufficient for the first 14 embryonic cell cycles and provide the developing embryo with sufficient histone proteins until the zygotic histone genes are activated. The maternally deposited histone mRNA is synthesized in stage 10b of oogenesis after completion of endoreduplication of the nurse cells. Histone mRNAs are the only cellular mRNAs that are not polyadenylated, ending instead in a conserved stemloop instead of a polyA tail. The Stem-loop binding protein (SLBP) binds the 3' end of histone mRNA and is essential for both the biosynthesis and translation of histone mRNA. We report that a 10 aa region in SLBP, which is not required for processing in vitro, is essential for transcription of histone mRNA in the stage 10b oocyte. In stage 10b the Histone Locus Bodies (HLBs) produce histone mRNAs in the absence of phosphorylation of Mxc, normally required for histone gene expression in S-phase cells. Mutants expressing this SLBP develop normally, produce small amounts of polyadenylated histone mRNA throughout development, but little histone mRNA in stage 10b resulting in death of the embryos in the first hr of development.

Natural tolerance to transposition is associated with double-strand break repair and germ-cell differentiation

“…Therefore, histone upregulation exhibited by sensitive alleles may reduce their tolerance to genotoxic stress resulting from P-element activity. Notably, the expression of both histone and chorion genes are increased in late oogenesis (Ambrosio & Schedl, 1985;Potter-Birriel et al, 2020;Ruddell & Jacobs-Lorena, 1985;Gail L. Waring, 2000), meaning that their inverted differential expression between sensitive and tolerant genotypes cannot be explained by differential abundance of late stage oocytes.…”

“…However, a careful inspection of genes underlying these enriched terms reveals that with the exception of translation, they are majorly explained by the increased expression of replication-dependent (RD) histone gene copies (Figure 2d). Notably, the expression of both histone and chorion genes are increased in late oogenesis [35][36][37][38], meaning that their inverted differential expression between sensitive and tolerant genotypes cannot be explained by differential abundance of late stage oocytes. Furthermore, histone upregulation may reduce tolerance to P-element activity, since overexpression of RD histones is associated with increased sensitivity to DNA damage [39][40][41][42][43], and excess Histones are reported to compete with DNA repair proteins for binding to damage sites [40].…”