Laboratoire de Biochimie Pharmaceutique Inserm U835 Upres EA2311 Université de Rennes, Rennes, France.
Nat Struct Mol Biol. 2011 Dec 25;19(1):105-12. doi: 10.1038/nsmb.2193.
Antisense RNAs (asRNAs) pair to RNAs expressed from the complementary strand, and their functions are thought to depend on nucleotide overlap with genes on the opposite strand. There is little information on the roles and mechanisms of asRNAs. We show that a cis asRNA acts in trans, using a domain outside its target complementary sequence. SprA1 small regulatory RNA (sRNA) and SprA1(AS) asRNA are concomitantly expressed in S. aureus. SprA1(AS) forms a complex with SprA1, preventing translation of the SprA1-encoded open reading frame by occluding translation initiation signals through pairing interactions. The SprA1 peptide sequence is within two RNA pseudoknots. SprA1(AS) represses production of the SprA1-encoded cytolytic peptide in trans, as its overlapping region is dispensable for regulation. These findings demonstrate that sometimes asRNA functional domains are not their gene-target complementary sequences, suggesting there is a need for mechanistic re-evaluation of asRNAs expressed in prokaryotes and eukaryotes.
反义 RNA(asRNA)与来自互补链的 RNA 配对,其功能被认为取决于与相反链上基因的核苷酸重叠。关于 asRNA 的作用和机制的信息很少。我们表明,顺式 asRNA 以反式作用,使用其靶互补序列之外的结构域。金黄色葡萄球菌中同时表达 SprA1 小调控 RNA(sRNA)和 SprA1(asRNA)。SprA1(asRNA)与 SprA1 形成复合物,通过配对相互作用封闭翻译起始信号,从而阻止 SprA1 编码的开放阅读框的翻译。SprA1 肽序列位于两个 RNA 假结内。SprA1(asRNA)通过反式抑制 SprA1 编码的细胞溶素肽的产生,因为其重叠区域对于调节是可有可无的。这些发现表明,有时 asRNA 的功能结构域不是其基因靶互补序列,这表明需要重新评估原核生物和真核生物中表达的 asRNA 的机制。