Mologni L, leCoutre P, Nielsen P E, Gambacorti-Passerini C
Division of Experimental Oncology D, Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Nucleic Acids Res. 1998 Apr 15;26(8):1934-8. doi: 10.1093/nar/26.8.1934.
The potential use of peptide nucleic acid (PNA) as a sequence-specific inhibitor of RNA translation is investigated in this report. Three different regions of the PML/RARalpha oncogene, including two AUG potential start codons, were studied as targets of translation inhibition by antisense PNA in a cell-free system. A PNA targeted to the second AUG start codon, which was shown previously to be able to suppress in vitro translation from that site completely, was used alone or in combination with another PNA directed to the first AUG, and a third PNA within the 5'-untranslated region (5'-UTR) of mRNA. When used alone, no PNA was able to completely block the synthesis of the PML/RARalpha protein. The 5'-UTR PNA was the most potent translation inhibitor when used as single agent. However, a near complete (>/=90%) specific inhibition of the PML/RARalpha gene was obtained when the three PNAs were used in combination, thus obtaining an additive antisense effect.
本报告研究了肽核酸（PNA）作为RNA翻译的序列特异性抑制剂的潜在用途。在无细胞系统中，研究了PML/RARα癌基因的三个不同区域，包括两个AUG潜在起始密码子，作为反义PNA翻译抑制的靶点。一种靶向第二个AUG起始密码子的PNA（先前已证明能够完全抑制该位点的体外翻译）单独使用或与另一种靶向第一个AUG的PNA以及mRNA 5'-非翻译区（5'-UTR）内的第三种PNA联合使用。单独使用时，没有一种PNA能够完全阻断PML/RARα蛋白的合成。5'-UTR PNA作为单一药物时是最有效的翻译抑制剂。然而，当三种PNA联合使用时，对PML/RARα基因获得了近乎完全（≥90%）的特异性抑制，从而获得了相加的反义效应。
