Le S Y, Maizel J V
Laboratory of Mathematical Biology, Division of Basic Sciences, National Cancer Institute, NIH, Building 469, Room 151, Frederick, MD 21702, USA.
Nucleic Acids Res. 1997 Jan 15;25(2):362-69. doi: 10.1093/nar/25.2.362.
The 5'-non-translated regions (5'NTR) of human immunoglobulin heavy chain binding protein (BiP), Antennapedia (Antp) ofDrosophilaand human fibroblast growth factor 2 (FGF-2) mRNAs are reported to mediate translation initiation by an internal ribosome binding mechanism. In this study, we investigate predicted features of the higher order structures folded in these 5'NTR sequences. Statistical analyses of RNA folding detected a 92 nt unusual folding region (UFR) from 129 to 220, close to the initiator AUG in the BiP mRNA. Details of the structural analyses show that the UFR forms a Y-type stem-loop structure with an additional stem-loop in the 3'-end resembling the common structure core found in the internal ribosome entry site (IRES) elements of picornavirus. The Y-type structural motif is also conserved among a number of divergent BiP mRNAs. We also find two RNA elements in the 5'-leader sequence of human FGF-2. The first RNA element (96 nt) is 2 nt upstream of the first CUG start codon located in the reported IRES element of human FGF-2. The second (107 nt) is immediately upstream of the authentic initiator AUG of the main open reading frame. Intriguingly, the folded RNA structural motif in the two RNA elements is conserved in other members of FGF family and shares the same structural features as that found in the 5'NTR of divergent BiP mRNAs. We suggest that the common RNA structural motif conserved in the diverse BiP and FGF-2 mRNAs has a general function in the internal ribosome binding mechanism of cellular mRNAs.
据报道，人免疫球蛋白重链结合蛋白（BiP）、果蝇触角足蛋白（Antp）和人成纤维细胞生长因子2（FGF - 2）mRNA的5'非翻译区（5'NTR）通过内部核糖体结合机制介导翻译起始。在本研究中，我们研究了这些5'NTR序列中折叠形成的高阶结构的预测特征。RNA折叠的统计分析在BiP mRNA中检测到一个从129至220位的92个核苷酸的异常折叠区域（UFR），靠近起始密码子AUG。结构分析的细节表明，UFR形成一个Y型茎环结构，其3'端还有一个茎环，类似于微小RNA病毒内部核糖体进入位点（IRES）元件中常见的结构核心。Y型结构基序在许多不同的BiP mRNA中也保守。我们还在人FGF - 2的5'前导序列中发现了两个RNA元件。第一个RNA元件（96个核苷酸）位于人FGF - 2报道的IRES元件中第一个CUG起始密码子上游2个核苷酸处。第二个（107个核苷酸）紧邻主要开放阅读框的真实起始密码子AUG上游。有趣的是，这两个RNA元件中折叠的RNA结构基序在FGF家族的其他成员中保守，并且与不同BiP mRNA的5'NTR中发现的结构基序具有相同的结构特征。我们认为，在不同BiP和FGF - 2 mRNA中保守的共同RNA结构基序在细胞mRNA的内部核糖体结合机制中具有普遍功能。
