A novel alternative splicing isoform of human T-cell leukemia virus type 1 bZIP factor (HBZ-SI) targets distinct subnuclear localization
A novel alternative splicing isoform of human T-cell leukemia virus type 1 bZIP factor (HBZ-SI) targets distinct subnuclear localization
复制标题
DOI：
10.1128/jvi.80.5.2495-2505.2006
复制
发表时间：
2006-03-01
影响因子：
5.4
通讯作者：
Kamihira, S
中科院分区：
文献类型：
--
作者：
Murata, K;Hayashibara, T;Kamihira, S
成人T细胞白血病（ATL）与先前感染人类T细胞白血病病毒I型（HTLV-1）有关;然而，HTLV-1导致成人T细胞白血病的机制尚未完全阐明。最近，在HTLV-1基因组负链（HBZ）中发现了一种功能性碱性亮氨酸拉链（bZIP）蛋白。本文报道了一种新的HTLV-1 bZIP因子（HBZ）亚型HBZ-SI，它是通过逆转录-PCR（RT-PCR）结合5'和3' cDNA末端快速扩增（RACE）鉴定的。HBZ-SI是一种206个氨基酸长的蛋白质，通过HBZ基因的一部分与位于HTLV-1基因组3'长末端重复序列中的新外显子之间的选择性剪接产生。因此，这些同种型共享> 95%的氨基酸序列同一性，并且仅在它们的N末端不同，表明HBZ-SI也是功能性蛋白质。双重RT-PCR和实时定量RT-PCR分析表明，这些亚型的mRTNA在所有检查的ATL细胞样品中以相等的水平表达。尽管如此，我们通过Western印迹发现HBZ-SI蛋白在所检测的一些ATL细胞系中优先表达。从这些亚型的亚细胞定位分析中获得了一个关键发现。尽管它们的高序列相似性，每个亚型的目标是可区分的亚核结构。这些数据显示了ATL细胞中存在一种新的HBZ亚型，此外，还揭示了每种亚型可能在细胞核的不同区域中发挥独特作用的可能性。
Adult T-cell leukemia (ATL) is associated with prior infection with human T-cell leukemia virus type I (HTLV-1); however, the mechanism by which HTLV-1 causes adult T-cell leukemia has not been fully elucidated. Recently, a functional basic leucine zipper (bZIP) protein coded in the minus strand of HTLV-1 genome (HBZ) was identified. We report here a novel isoform of the HTLV-1 bZIP factor (HBZ), HBZ-SI, identified by means of reverse transcription -PCR (RT-PCR) in conjunction with 5' and 3' rapid amplification of cDNA ends (RACE). HBZ-SI is a 206-amino-acid-long protein and is generated by alternative splicing between part of the HBZ gene and a novel exon located in the 3' long terminal repeat of the HTLV-1 genome. Consequently, these isoforms share > 95% amino acid sequence identity, and differ only at their N termini, indicating that HBZ-SI is also a functional protein. Duplex RT-PCR and real-time quantitative RT-PCR analyses showed that the mRTNAs of these isoforms were expressed at equivalent levels in all ATL cell samples examined. Nonetheless, we found by Western blotting that the HBZ-SI protein was preferentially expressed in some ATL cell lines examined. A key finding was obtained from the subcellular localization analyses of these isoforms. Despite their high sequence similarity, each isoform was targeted to distinguishable subnuclear structures. These data show the presence of a novel isoform of HBZ in ATL cells, and in addition, shed new light on the possibility that each isoform may play a unique role in distinct regions in the cell nucleus.