Department of Microbiology, University of Calcutta, University College of Science and Technology, Kolkata, India.
FEBS Lett. 2011 Oct 20;585(20):3348-53. doi: 10.1016/j.febslet.2011.09.026. Epub 2011 Sep 29.
HBV particles with genome derived from spliced mRNAs accumulate in patients with virus-derived severe liver necrosis and fibrosis. We investigated the role of an intronic element (intronic splicing silencer-long, ISS(L)) on splicing of HBV minigene transcripts. Removal of the entire ISS(L) showed two-fold increase in splicing while shorter deletions within ISS(L) indicated isolated clusters of activator and repressor domains. Activator domains stimulated splicing in presence of PRE, a long HBV 3' exon and even when present in a heterologous context. Mutations in the repressor domain unexpectedly augmented repression. The role of this intronic splicing regulatory element could be important for HBV pathogenesis.
HBV 颗粒的基因组来源于拼接的 mRNAs，在病毒引起的严重肝坏死和纤维化的患者中积累。我们研究了内含子元件（内含子剪接沉默子长，ISS(L)) 在 HBV 基因转录物剪接中的作用。去除整个 ISS(L) 会使剪接增加两倍，而在 ISS(L) 内的较短缺失则表明激活和抑制域的孤立簇。在 PRE（HBV 3' 外显子的长序列）存在的情况下，激活域刺激剪接，即使在异源环境中也是如此。在抑制域中突变出乎意料地增强了抑制作用。这种内含子剪接调控元件的作用可能对 HBV 发病机制很重要。
