Pre-mRNA processing of the replication-dependent canonical histone mRNAs requires an endonucleolytic cleavage immediately after a conserved stem loop structure which occurs before RNA Pol II encounters any poly(A) signal. Thus, in contrast to all other eukaryotic mRNAs, the canonical histone mRNAs are not polyadenylated in their 3′ ends. The binding of stem-loop binding protein (SLBP) to the stem loop structure of the histone mRNAs is required for this process. SLBP is also involved in regulation of histone mRNA nuclear export, degradation, and translation. Depletion of SLBP has been shown to induce polyadenylation of histone mRNAs and alteration of histone protein levels, which are considered to contribute to the observed aberrant cell cycle progress and genomic instability resulting from the loss of SLBP function. Recent studies have demonstrated that some heavy metal carcinogens, including arsenic and nickel, can induce the loss of SLBP and the gain of polyadenylation of canonical histone mRNAs. Polyadenylated canonical histone H3 can result in abnormal transcription, cell cycle arrest, genomic instability, and cell transformation, which links SLBP depletion and subsequent histone mRNA misprocessing to cancer. This review seeks to briefly summarize what is known about regulation of SLBP expression, consequences of SLBP depletion, its roles in cancer-related end points, with particular focus on metal-induced SLBP depletion and the potential of SLBP depletion as a new mechanism for metal-induced carcinogenesis.

复制依赖性典型组蛋白 mRNA 的前 mRNA 加工需要在保守的茎环结构之后立即进行核酸内切切割，该切割发生在 RNA Pol II 遇到任何 Poly(A) 信号之前。因此，与所有其他真核 mRNA 相比，规范组蛋白 mRNA 的 3' 末端并未聚腺苷酸化。此过程需要茎环结合蛋白 (SLBP) 与组蛋白 mRNA 的茎环结构的结合。SLBP 还参与组蛋白 mRNA 核输出、降解和翻译的调节。SLBP 的缺失已被证明会诱导组蛋白 mRNA 的多腺苷酸化和组蛋白蛋白水平的改变，这被认为是导致观察到的由于 SLBP 功能丧失而导致的异常细胞周期进展和基因组不稳定的原因。最近的研究表明，一些重金属致癌物，包括砷和镍，可以诱导 SLBP 的丧失和典型组蛋白 mRNA 多腺苷酸化的增加。多腺苷酸化典型组蛋白 H3 可导致异常转录、细胞周期停滞、基因组不稳定和细胞转化，从而将 SLBP 耗竭和随后的组蛋白 mRNA 错误加工与癌症联系起来。本综述旨在简要总结 SLBP 表达调节的已知信息、SLBP 耗竭的后果、其在癌症相关终点中的作用，特别关注金属诱导的 SLBP 耗竭以及 SLBP 耗竭作为金属新机制的潜力。 -诱发癌变。