Department of Biology, University of Colorado, Colorado Springs, Colorado, USA.
Department of Molecular Biology, Colorado College, Colorado Springs, Colorado, USA.
mBio. 2022 Feb 22;13(1):e0344321. doi: 10.1128/mbio.03443-21. Epub 2022 Jan 11.
Despite their ubiquitous nature, few antisense RNAs have been functionally characterized, and this class of RNAs is considered by some to be transcriptional noise. Here, we report that an antisense RNA (asRNA), aMEF (antisense ), functions as a dual regulator for the type II toxin-antitoxin (TA) system . Unlike type I TA systems and many other regulatory asRNAs, aMEF stimulates the synthesis and translation of rather than inhibition and degradation. Our data indicate that a double-stranded RNA intermediate and RNase III are not necessary for aMEF-dependent regulation of expression. The lack of conservation of asRNA promoters has been used to support the hypothesis that asRNAs are spurious transcriptional noise and nonfunctional. We demonstrate that the aMEF promoter is active and functional in Escherichia coli despite poor sequence conservation, indicating that the lack of promoter sequence conservation should not be correlated with functionality. Next-generation RNA sequencing of numerous organisms has revealed that transcription is widespread across the genome, termed pervasive transcription, and does not adhere to annotated gene boundaries. The function of pervasive transcription is enigmatic and has generated considerable controversy as to whether it is transcriptional noise or biologically relevant. Antisense transcription is one class of pervasive transcription that occurs from the DNA strand opposite an annotated gene. Relatively few pervasively transcribed asRNAs have been functionally characterized, and their regulatory roles or lack thereof remains unknown. It is important to study examples of these asRNAs and determine if they are functional regulators. In this study, we elucidate the function of an asRNA (aMEF) demonstrating that pervasive transcripts can be functional.
尽管反义 RNA（asRNA）普遍存在，但很少有反义 RNA 具有功能特征，一些人认为这种 RNA 是转录噪声。在这里，我们报告了一种反义 RNA（asRNA），aMEF（反义），作为 II 型毒素-抗毒素（TA）系统的双重调节剂。与 I 型 TA 系统和许多其他调节性 asRNA 不同，aMEF 刺激而不是抑制和降解 的合成和翻译。我们的数据表明，双链 RNA 中间体和 RNase III 不是 aMEF 依赖调节 表达所必需的。反义 RNA 启动子缺乏保守性已被用于支持反义 RNA 是虚假转录噪声和无功能的假说。我们证明，尽管启动子序列的保守性很差，aMEF 启动子在大肠杆菌中是活跃和功能的，这表明启动子序列保守性的缺乏不应与功能相关。对许多生物体的下一代 RNA 测序表明，转录广泛存在于基因组中，称为普遍转录，并且不遵守注释基因边界。普遍转录的功能是神秘的，并且关于它是转录噪声还是具有生物学相关性产生了相当大的争议。反义转录是从注释基因的 DNA 链的相反链发生的普遍转录的一类。相对较少的普遍转录的 asRNA 已具有功能特征，其调节作用或缺乏仍然未知。研究这些 asRNA 的实例并确定它们是否具有功能调节作用非常重要。在这项研究中，我们阐明了反义 RNA（aMEF）的功能，证明了普遍转录物可以是功能性的。
