A Kaposi's sarcoma virus RNA element that increases the nuclear abundance of intronless transcripts

A Kaposi's sarcoma virus RNA element that increases the nuclear abundance of intronless transcripts
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DOI:
10.1038/sj.emboj.7600662
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发表时间:
2005-05-18
期刊:
影响因子:
11.4
通讯作者:
Steitz, JA
Steitz, JA
中科院分区:
生物学1区
文献类型:
--
作者:
Conrad, NK;Steitz, JA

文献摘要

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卡波西肉瘤相关疱疹病毒产生一种1077个核苷酸的非编码、多腺化、专一核RNA,称为PAN,在裂解感染的细胞中高度表达。我们报道了PAN含有一个新的转录后元件,对其丰富的积累是必不可少的。PAN-ENE(PAN RNA表达和核保持元件)提高了体内3‘端形成的效率,并足以增加原本表达效率低下的无内含子β-珠蛋白结构的RNA丰度。PAN-ENE不会同时增加编码蛋白的产量。相反,它在细胞核中保留了未剪接的β-珠蛋白mRNA。出口因素的捆绑可以超过泛ENE的核保留,从而支持一种机制,从而使PAN-ENE阻止组装具有出口能力的mRNP。PAN-ENE的活性是无内含子结构所特有的,因为将PAN-ENE插入到拼接的β-珠蛋白结构中不会影响mRNA的丰度,也不会影响定位。这是第一次表征顺式作用元件,它增加了无内含子转录本的RNA丰度,但抑制了具有出口能力的mRNP的组装。
The Kaposi's sarcoma-associated herpesvirus produces a 1077 nucleotide noncoding, polyadenylated, exclusively nuclear RNA called PAN that is highly expressed in lytically infected cells. We report that PAN contains a novel post-transcriptional element essential for its abundant accumulation. The element, PAN-ENE (PAN RNA expression and nuclear retention element), increases the efficiency of 3'-end formation in vivo and is sufficient to enhance RNA abundance from an otherwise inefficiently expressed intronless beta-globin construct. The PAN-ENE does not concomitantly increase the production of encoded protein. Rather, it retains the unspliced beta-globin mRNA in the nucleus. Tethering of export factors can override the nuclear retention of the PAN-ENE, supporting a mechanism whereby the PAN-ENE blocks assembly of an export-competent mRNP. The activities of the PAN-ENE are specific to intronless constructs, since inserting the PAN-ENE into a spliced beta-globin construct has no effect on mRNA abundance and does not affect localization. This is the first characterization of a cis-acting element that increases RNA abundance of intronless transcripts but inhibits assembly of an export-competent mRNP.