Howard Hughes Medical Institute, Yale University, New Haven, CT 06520-8103, USA.
Genome Biol. 2010;11(3):R31. doi: 10.1186/gb-2010-11-3-r31. Epub 2010 Mar 15.
Structured noncoding RNAs perform many functions that are essential for protein synthesis, RNA processing, and gene regulation. Structured RNAs can be detected by comparative genomics, in which homologous sequences are identified and inspected for mutations that conserve RNA secondary structure.
By applying a comparative genomics-based approach to genome and metagenome sequences from bacteria and archaea, we identified 104 candidate structured RNAs and inferred putative functions for many of these. Twelve candidate metabolite-binding RNAs were identified, three of which were validated, including one reported herein that binds the coenzyme S-adenosylmethionine. Newly identified cis-regulatory RNAs are implicated in photosynthesis or nitrogen regulation in cyanobacteria, purine and one-carbon metabolism, stomach infection by Helicobacter, and many other physiological processes. A candidate riboswitch termed crcB is represented in both bacteria and archaea. Another RNA motif may control gene expression from 3'-untranslated regions of mRNAs, which is unusual for bacteria. Many noncoding RNAs that likely act in trans are also revealed, and several of the noncoding RNA candidates are found mostly or exclusively in metagenome DNA sequences.
This work greatly expands the variety of highly structured noncoding RNAs known to exist in bacteria and archaea and provides a starting point for biochemical and genetic studies needed to validate their biologic functions. Given the sustained rate of RNA discovery over several similar projects, we expect that far more structured RNAs remain to be discovered from bacterial and archaeal organisms.
结构非编码 RNA 具有多种功能,这些功能对于蛋白质合成、RNA 加工和基因调控都是必不可少的。结构 RNA 可以通过比较基因组学来检测,在比较基因组学中,识别同源序列并检查保守 RNA 二级结构的突变。
通过将基于比较基因组学的方法应用于细菌和古菌的基因组和宏基因组序列,我们鉴定了 104 个候选结构 RNA,并推断了其中许多的可能功能。鉴定了 12 个候选代谢物结合 RNA,其中 3 个得到了验证,包括本文报道的一个结合辅酶 S-腺苷甲硫氨酸的 RNA。新鉴定的顺式调控 RNA 与蓝细菌中的光合作用或氮调节、嘌呤和一碳代谢、幽门螺杆菌引起的胃部感染以及许多其他生理过程有关。一个称为 crcB 的候选核糖开关存在于细菌和古菌中。另一个 RNA 基序可能控制 mRNA 3'-非翻译区的基因表达,这在细菌中是不常见的。还揭示了许多可能在转录中起作用的非编码 RNA,并且一些非编码 RNA 候选物主要或完全存在于宏基因组 DNA 序列中。
这项工作大大扩展了已知存在于细菌和古菌中的高度结构化非编码 RNA 的种类,并为验证其生物学功能所需的生化和遗传研究提供了起点。考虑到在几个类似项目中 RNA 发现的持续速度,我们预计从细菌和古菌生物中还会发现更多的结构 RNA。