Drosophila stem loop binding protein coordinates accumulation of mature histone mRNA with cell cycle progression
Drosophila stem loop binding protein coordinates accumulation of mature histone mRNA with cell cycle progression
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DOI：
10.1101/gad.862801
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发表时间：
2001-01-15
影响因子：
10.5
通讯作者：
Duronio, RJ
中科院分区：
文献类型：
--
作者：
Sullivan, E;Santiago, C;Duronio, RJ
复制相关的组蛋白基因编码唯一缺少polyA尾的后生动物mRNA，而是以形成茎环的保守的26-nt序列结束。哺乳动物组蛋白mRNA的大部分调节是转录后的，并由这个独特的3'端介导。茎环结合蛋白（SLBP）与组蛋白mRNA的3'端结合，参与组蛋白mRNA代谢的各个方面，包括细胞周期调控。为了从遗传学角度研究SLBP的功能，我们用酵母三杂交法克隆了果蝇SLBP的编码基因（dSLBP），并分离了dSLB中的突变。dSLBP功能是合子和母体都需要的。强dSLBP等位基因在发育后期引起合子致死，并导致在非复制细胞中积累的稳定组蛋白mRNA的产生。这些组蛋白mRNA是细胞质的，并且像其他聚合酶II转录物一样具有聚腺苷酸化的3'末端。亚型dSLBP等位基因支持合子发育，但导致雌性不育。来自这些雌性的卵含有显著降低的组蛋白mRNA水平，并且突变的胚胎不能完成合胞体胚胎周期。这部分是因为有丝分裂时染色体凝聚失败，阻碍了正常的后期。这些数据表明，体内组蛋白前mRNA的3'端加工需要dSLBP，并且这是发育的基本功能。此外，dSLBP依赖性加工在将组蛋白mRNA产生与细胞周期偶联中起重要作用。
Replication-associated histone genes encode the only metazoan mRNAs that lack polyA tails, ending instead in a conserved 26-nt sequence that forms a stem-loop. Most of the regulation of mammalian histone mRNA is posttranscriptional and mediated by this unique 3' end. Stem-loop-binding protein (SLBP) binds to the histone mRNA 3' end and is thought to participate in all aspects of histone mRNA metabolism, including cell cycle regulation. To examine SLBP function genetically, we have cloned the gene encoding Drosophila SLBP (dSLBP) by a yeast three-hybrid method and have isolated mutations in dSLB. dSLBP function is required both zygotically and maternally. Strong dSLBP alleles cause zygotic lethality late in development and result in production of stable histone mRNA that accumulates in nonreplicating cells. These histone mRNAs are cytoplasmic and have polyadenylated 3' ends like other polymerase II transcripts. Hypomorphic dSLBP alleles support zygotic development but cause female sterility. Eggs from these females contain dramatically reduced levels of histone mRNA, and mutant embryos are not able to complete the syncytial embryonic cycles. This is in part because of a failure of chromosome condensation at mitosis that blocks normal anaphase. These data demonstrate that dSLBP is required in vivo for 3' end processing of histone pre-mRNA, and that this is an essential function for development. Moreover, dSLBP-dependent processing plays an important role in coupling histone mRNA production with the cell cycle.