SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs

There are two well-documented trans-acting factors required for histone pre-mRNA processing. These are:<p>1 Stem-loop binding protein (SLBP), also termed hairpin binding protein (HBP). This 32 kDa protein is likely the first protein that binds to the histone pre-mRNA as it is being transcribed. <p>The U7 snRNP. This particle contains the U7 snRNA, the smallest of the snRNAs which varies from 57-70 nts long depending on the species. The 5' end of U7 snRNA binds to a sequence 3' of the stemloop, termed the histone downstream element (HDE). There are a number of proteins found in the U7 snRNP. There are 7 Sm proteins, as are present in the spliceosomal snRNP. Five of these proteins are the same as ones found in the spliceosomal snRNPs and there are 2, Lsm10 and Lsm11 that are unique to U7 snRNP.<p> A third protein joins the U7 snRNP, ZFP100, a large zinc finger protein. ZFP100 interacts with SLBP bound to the histone pre-mRNA and with Lsm11 and likely plays a critical role in recruiting U7 snRNP to the histone pre-mRNA.<p> It should be noted that there must be other trans-acting factors, including the factor that catalyzes the cleavage reaction. The cleavage occurs in the presence of EDTA as does the cleavage reaction in polyadenylation, it is likely that this reaction is catalyzed by a protein. There may well be additional proteins associated with U7 snRNP, and since under some conditions in vitro processing occurs in the absence of SLBP, it is possible that all of the other factors required for processing are associated with the active form of U7 snRNP.

存在两种对组蛋白前mRNA加工至关重要的转录因子。这些因子包括：<p>1. 针环结合蛋白（SLBP），亦称发夹结合蛋白（HBP）。该32 kDa的蛋白质可能在转录过程中作为首批与组蛋白前mRNA结合的蛋白质。<p>U7小核RNA颗粒。该颗粒包含U7小核RNA，它是snRNA中最小的一种，长度介于57-70 nts之间，具体取决于物种。U7小核RNA的5'端与茎环的3'端序列结合，称为组蛋白下游元件（HDE）。U7小核RNA颗粒中存在多种蛋白质。其中包含7种Sm蛋白，与spliceosomal snRNP中的Sm蛋白相同。其中5种蛋白与spliceosomal snRNPs中的蛋白相同，另有2种，即Lsm10和Lsm11，为U7 snRNP所特有。<p>第三种蛋白质与U7 snRNP结合，即ZFP100，一种大型的锌指蛋白。ZFP100与结合在组蛋白前mRNA上的SLBP以及与Lsm11相互作用，可能在其招募U7 snRNP至组蛋白前mRNA中发挥关键作用。<p>值得注意的是，必须存在其他转录因子，包括催化裂解反应的因子。裂解反应在EDTA的存在下进行，与多聚腺苷酸化过程中的裂解反应相似，因此推测该反应可能由蛋白质催化。可能存在与U7 snRNP相关的其他蛋白质。鉴于在某些体外条件下，即使在没有SLBP的情况下也能进行加工，因此所有其他加工所需的因子可能都与U7 snRNP的活性形式相关。