Institut Jacques Monod, Université Paris Diderot, CNRS, Bâtiment Buffon, 15 rue Hélène Brion, 75205 Paris Cedex 13, France.
Mol Cell. 2012 Jan 13;45(1):132-9. doi: 10.1016/j.molcel.2011.12.011.
Histone H2B ubiquitylation is a transcription-dependent modification that not only regulates nucleosome dynamics but also controls the trimethylation of histone H3 on lysine 4 by promoting ubiquitylation of Swd2, a component of both the histone methyltransferase COMPASS complex and the cleavage and polyadenylation factor(CPF). We show that preventing either H2B ubiquitylation or H2B-dependent modification of Swd2 results in nuclear accumulation of poly(A) RNA due to a defect in the integrity and stability of APT, a subcomplex of the CPF. Ubiquitin-regulated APT complex dynamics is required for the correct recruitment of the mRNA export receptor Mex67 to nuclear mRNPs. While H2B ubiquitylation controls the recruitment of the different Mex67 adaptors to mRNPs, the effect of Swd2 ubiquitylation is restricted to Yra1 and Nab2, which, in turn, controls poly(A) tail length. Modification of H2B thus participates in the crosstalk between cotranscriptional events and assembly of mRNPs linking nuclear processing and mRNA export.
组蛋白 H2B 泛素化是一种转录依赖性修饰，不仅调节核小体动力学，还通过促进 Swd2 的泛素化来控制组蛋白 H3 赖氨酸 4 的三甲基化，Swd2 是组蛋白甲基转移酶 COMPASS 复合物和切割和多腺苷酸化因子 (CPF) 的组成部分。我们表明，防止 H2B 泛素化或 H2B 对 Swd2 的依赖性修饰都会导致 poly(A) RNA 的核积累，这是由于 CPF 的一个亚基 APT 的完整性和稳定性缺陷所致。泛素调节的 APT 复合物动力学对于正确募集 mRNA 出口受体 Mex67 到核 mRNPs 是必需的。虽然 H2B 泛素化控制不同 Mex67 衔接子到 mRNPs 的募集，但 Swd2 泛素化的作用仅限于 Yra1 和 Nab2，它们反过来控制 poly(A) 尾巴的长度。因此，H2B 的修饰参与了核转录事件和 mRNPs 组装之间的串扰，将核加工与 mRNA 输出联系起来。
