Comparative genomics of metabolic capacities of regulons controlled by cis-regulatory RNA motifs in bacteria

Sun, Eric I.; Leyn, Semen A.; Kazanov, Marat D.; Saier, Milton H.; Novichkov, Pavel S.; Rodionov, Dmitry A.

doi:10.1186/1471-2164-14-597

Comparative genomics of metabolic capacities of regulons controlled by cis-regulatory RNA motifs in bacteria

Journal Article · Mon Sep 02 00:00:00 EDT 2013 · BMC Genomics

DOI:https://doi.org/10.1186/1471-2164-14-597· OSTI ID:1626422

Sun, Eric I. ^[1]; Leyn, Semen A. ^[2]; Kazanov, Marat D. ^[3]; Saier, Milton H. ^[4]; Novichkov, Pavel S. ^[5]; Rodionov, Dmitry A. ^[2]

Univ. of California, San Diego, CA (United States). Division of Biological Sciences. Dept. of Molecular Biology; DOE/OSTI
Sanford-Burnham Medical Research Inst., La Jolla, CA (United States); Russian Academy of Sciences (RAS), Moscow (Russian Federation). Inst. for Information Transmission Problems (IITP)
Russian Academy of Sciences (RAS), Moscow (Russian Federation). Inst. for Information Transmission Problems (IITP)
Univ. of California, San Diego, CA (United States). Division of Biological Sciences. Dept. of Molecular Biology
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Background: 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. Results: 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. Conclusions: 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/).

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231; SC0004999

OSTI ID:: 1626422

Journal Information:: BMC Genomics, Journal Name: BMC Genomics Journal Issue: 1 Vol. 14; ISSN 1471-2164

Publisher:: SpringerCopyright Statement

Country of Publication:: United States

Language:: English

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