Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.
Mol Carcinog. 2010 Mar;49(3):215-23. doi: 10.1002/mc.20591.
Parafibromin, encoded by the gene HRPT2, is a tumor suppressor protein associated with the RNA polymerase II-associated complex, Paf1 complex. HRPT2 mutations were first identified in patients with the multiple endocrine neoplasia syndrome, hyperparathyroidism-jaw tumor (HPT-JT) syndrome, and have also been found in sporadic parathyroid and renal tumors. However, the mechanisms by which parafibromin suppresses tumor formation remain unknown. In this study, we identify a novel role of parafibromin in the regulation of replication-dependent histones. Both in vitro and in vivo analyses reveal a posttranscriptional role of parafibromin in histone mRNA processing. Downregulation of parafibromin through RNA interference or in vivo mutations lead to uncleaved histone mRNA with polyadenylated tails. These results indicate that parafibromin regulates the 3' processing of histone RNA, an essential component of the cell cycle.
parafibromin，由基因 HRPT2 编码，是一种与 RNA 聚合酶 II 相关复合物、Paf1 复合物相关的肿瘤抑制蛋白。HRPT2 突变首先在多发性内分泌肿瘤综合征、甲状旁腺-颌骨肿瘤（HPT-JT）综合征患者中被发现，也在散发性甲状旁腺和肾肿瘤中被发现。然而，parafibromin 抑制肿瘤形成的机制尚不清楚。在这项研究中，我们确定了 parafibromin 在调节复制依赖性组蛋白方面的一个新作用。体外和体内分析都揭示了 parafibromin 在组蛋白 mRNA 加工中的转录后作用。通过 RNA 干扰或体内突变下调 parafibromin 会导致带有多聚腺苷酸尾巴的未切割组蛋白 mRNA。这些结果表明 parafibromin 调节组蛋白 RNA 的 3' 加工，这是细胞周期的一个重要组成部分。
