Sanford-Burnham Medical Research Institute, 92037 La Jolla, CA, USA.
BMC Genomics. 2013 Sep 2;14:597. doi: 10.1186/1471-2164-14-597.
In silico comparative genomics approaches have been efficiently used for functional prediction and reconstruction of metabolic and regulatory networks. Riboswitches are metabolite-sensing structures often found in bacterial mRNA leaders controlling gene expression on transcriptional or translational levels.An increasing number of riboswitches and other cis-regulatory RNAs have been recently classified into numerous RNA families in the Rfam database. High conservation of these RNA motifs provides a unique advantage for their genomic identification and comparative analysis.
A comparative genomics approach implemented in the RegPredict tool was used for reconstruction and functional annotation of regulons controlled by RNAs from 43 Rfam families in diverse taxonomic groups of Bacteria. The inferred regulons include ~5200 cis-regulatory RNAs and more than 12000 target genes in 255 microbial genomes. All predicted RNA-regulated genes were classified into specific and overall functional categories. Analysis of taxonomic distribution of these categories allowed us to establish major functional preferences for each analyzed cis-regulatory RNA motif family. Overall, most RNA motif regulons showed predictable functional content in accordance with their experimentally established effector ligands. Our results suggest that some RNA motifs (including thiamin pyrophosphate and cobalamin riboswitches that control the cofactor metabolism) are widespread and likely originated from the last common ancestor of all bacteria. However, many more analyzed RNA motifs are restricted to a narrow taxonomic group of bacteria and likely represent more recent evolutionary innovations.
The reconstructed regulatory networks for major known RNA motifs substantially expand the existing knowledge of transcriptional regulation in bacteria. The inferred regulons can be used for genetic experiments, functional annotations of genes, metabolic reconstruction and evolutionary analysis. The obtained genome-wide collection of reference RNA motif regulons is available in the RegPrecise database (http://regprecise.lbl.gov/).
计算比较基因组学方法已被有效地用于功能预测和代谢及调控网络的重建。核糖开关是经常在细菌 mRNA 前导区发现的代谢物感应结构，可在转录或翻译水平上控制基因表达。越来越多的核糖开关和其他顺式调控 RNA 最近已在 Rfam 数据库中被分类为数个 RNA 家族。这些 RNA 基序的高度保守性为它们的基因组识别和比较分析提供了独特的优势。
在 RegPredict 工具中实现的计算比较基因组学方法用于重建和功能注释由 43 个 Rfam 家族的 RNA 在不同分类群的细菌中调控的调控子。推断的调控子包括 255 个微生物基因组中约 5200 个顺式调控 RNA 和 12000 多个靶基因。所有预测的 RNA 调控基因被分类为特定和总体功能类别。这些类别的分类分析使我们能够确定每个分析的顺式调控 RNA 基序家族的主要功能偏好。总体而言，大多数 RNA 基序调控子表现出与其实验确定的效应配体一致的可预测功能内容。我们的结果表明，一些 RNA 基序（包括控制辅助因子代谢的硫胺素焦磷酸和钴胺素核糖开关）广泛存在，可能起源于所有细菌的最后共同祖先。然而，更多分析的 RNA 基序仅限于细菌的一个狭窄分类群，可能代表最近的进化创新。
主要已知 RNA 基序的重建调控网络极大地扩展了细菌中转录调控的现有知识。推断的调控子可用于遗传实验、基因功能注释、代谢重建和进化分析。在 RegPrecise 数据库（http://regprecise.lbl.gov/）中提供了获得的广泛的参考 RNA 基序调控子基因组数据集。
