A dual upstream open reading frame-based autoregulatory circuit controlling polyamine-responsive translation
A dual upstream open reading frame-based autoregulatory circuit controlling polyamine-responsive translation
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DOI：
10.1074/jbc.m509340200
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发表时间：
2005-11-25
影响因子：
4.8
通讯作者：
Michael, AJ
中科院分区：
文献类型：
--
作者：
Hanfrey, C;Elliott, KA;Michael, AJ
描述了关键多胺生物合成酶S-腺苷甲硫氨酸脱羧酶（S-腺苷甲硫氨酸脱羧酶）的一种新的翻译调节形式。植物MetDC mRNA 5'前导序列含有两个高度保守的重叠上游开放阅读框（uORF）：5'微小uORF和3'小型uORF。我们证明，小的uORF编码的肽是负责组成型抑制下游翻译的cDNAMetDC酶原ORF的情况下，增加多胺水平。在植物中描述的序列依赖性uORF的第一个实例在酿酒酵母中也是有功能的。微小的uORF是正常的多胺反应性的mammal-MetDC mRNA翻译所需的，我们提出，这是通过控制核糖体识别的闭塞的小uORF，无论是通过核糖体泄漏扫描或程序化的-1移码。体外表达表明，微小和小的uORF都被翻译。这种微小/小uORF构型从苔藓到拟南芥是高度保守的，并且在单细胞绿色衣藻（Chlamycellus reinhardtii）的MetDC mRNA 5'前导序列中发现了更加分歧的微小/小uORF排列，表明uORF的古老起源。
A novel form of translational regulation is described for the key polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC). Plant AdoMetDC mRNA 5' leaders contain two highly conserved overlapping upstream open reading frames (uORFs): the 5' tiny and 3' small uORFs. We demonstrate that the small uORF-encoded peptide is responsible for constitutively repressing downstream translation of the AdoMetDC proenzyme ORF in the absence of increased polyamine levels. This first example of a sequence-dependent uORF to be described in plants is also functional in Saccharomyces cerevisiae. The tiny uORF is required for normal polyamine-responsive AdoMetDC mRNA translation, and we propose that this is achieved by control of ribosomal recognition of the occluded small uORF, either by ribosomal leaky scanning or by programmed -1 frameshifting. In vitro expression demonstrated that both the tiny and the small uORFs are translated. This tiny/small uORF configuration is highly conserved from moss to Arabidopsis thaliana, and a more diverged tiny/small uORF arrangement is found in the AdoMetDC mRNA 5' leader of the single-celled green alga Chlamydomonas reinhardtii, indicating an ancient origin for the uORFs.