Nucleic Acids Research Advance Access originally published online on November 16, 2008
Nucleic Acids Research 2009 37(Database issue):D150-D154; doi:10.1093/nar/gkn852
Nucleic Acids Research, 2009, Vol. 37, Database issue D150-D154
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
sRNAMap: genomic maps for small non-coding RNAs, their regulators and their targets in microbial genomes
Hsi-Yuan Huang1,
Heng-Yi Chang1,
Chih-Hung Chou2,
Ching-Ping Tseng2,3,
Shinn-Ying Ho1,3,
Chi-Dung Yang3,
Yih-Wei Ju3 and
Hsien-Da Huang1,3,4,*
1Institute of Bioinformatics and Systems Biology, 2Institute of Molecular Medicine and Bioengineering, 3Department of Biological Science and Technology and 4Core Facility for Structural Bioinformatics, National Chiao Tung University, Hsin-Chu 300, Taiwan
*To whom correspondence should be addressed. Tel: +886 3 5712121 Ext. 56952; Fax: +886 3 5729288; Email: bryan{at}mail.nctu.edu.tw
Received August 20, 2008. Revised October 9, 2008. Accepted October 16, 2008.
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ABSTRACT
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Small non-coding RNAs (sRNAs) carry out a variety of biological
functions and affect protein synthesis and protein activities
in prokaryotes. Recently, numerous sRNAs and their targets were
identified in
Escherichia coli and in other bacteria. It is
crucial to have a comprehensive resource concerning the annotation
of small non-coding RNAs in microbial genomes. This work presents
an integrated database, namely sRNAMap, to collect the sRNA
genes, the transcriptional regulators of sRNAs and the sRNA
target genes by integrating a variety of biological databases
and by surveying literature. In this resource, we collected
397 sRNAs, 62 regulators/sRNAs and 60 sRNAs/targets in 70 microbial
genomes. Additionally, more valuable information of the sRNAs,
such as the secondary structure of sRNAs, the expressed conditions
of sRNAs, the expression profiles of sRNAs, the transcriptional
start sites of sRNAs and the cross-links to other biological
databases, are provided for further investigation. Besides,
various textual and graphical interfaces were designed and implemented
to facilitate the data access in sRNAMap. sRNAMap is available
at
http://sRNAMap.mbc.nctu.edu.tw/.
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INTRODUCTION
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Small non-coding RNAs (sRNAs), which are discovered in many
organisms ranging from bacteria to mammals, play important regulatory
roles in cell physiology including regulation of cell development,
cell death and chromosome silencing (
1). Many of them regulate
gene expression at a posttranscriptional level, either by acting
as antisense RNAs, by binding to complementary sequences of
target transcripts, or by interacting with proteins (
2).
Figure 1 depicts the synthesis and the functions of small non-coding
RNAs. The transcription of sRNAs is regulated by transcription
factors. Furthermore, sRNAs can play regulatory roles in translation
repression, translation activation, mRNA degradation and mRNA
stability.
EcoCyc (
3) and RegulonDB (
4) integrate biological knowledge
of the transcriptional regulation in
Escherichia coli, as well
as knowledge on the organization of the genes and regulatory
signals into operons in the chromosome. ASAP (
5) is developed
to store genome sequences in conjunction with associated annotations
and functional characterization data. NONCODE (
6) is an integrated
knowledge database dedicated to non-coding RNAs. In addition,
Storz
et al. (
7) used northern blotting analysis to document
a total of 79 small RNAs in
E. coli.
The increased investigations of important regulatory roles for sRNAs encoded far from their targets, acting on multiple targets, or both, has expanded interest in how to find such regulatory RNAs and how they work (8). Therefore, a resource collects the comprehensive annotation of small non-coding RNAs is crucial. We present an integrated database, sRNAMap, to collect the annotations of the sRNAs and the regulatory relationship between transcriptional regulator and sRNA, and between sRNA and its target genes. The design concept of the sRNAMap is illustrated in Figure 1. Additionally, more valuable information of sRNAs, such as the secondary structure of sRNAs, the expressed conditions of sRNAs, the expression profiles of sRNAs, the transcriptional start sites of sRNAs and the cross-links to other biological databases, are provided for further investigation. Besides, various textual and graphical interfaces were designed and implemented to facilitate the data access in sRNAMap.
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DATABASE STATISTICS
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The sRNAMap currently collects 397 sRNA genes, 62 regulator/sRNA
regulations and 60 sRNA/target regulations in seventy microbial
genomes. The detailed list of genome is given in
Table S4. As
given in
Table 1, for instance, the number of experimentally
validated sRNA genes in
E. coli,
Shigella boydii,
Shigella flexneri and
Yersinia pestis are 87, 35, 40 and 24, respectively.
Table 2 gives the length distribution of the total known sRNA genes.
Moreover, the sRNAMap analysed the transcriptional start sites
of sRNA genes.
Figure S3 (see
Supplementary Materials) is the
schematic diagram for the classification of transcription start
sites of sRNA. In
E. coli K-12 MG1655, 30 sRNAs have transcription
start sites and 33 sRNAs have 49 putative transcription start
sites, as given in
Table S5.
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DATA GENERATION
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The data generation flow of sRNAMap database is depicted in
Figure 2. The data generation flow comprises two major parts:
(i) integration of external data sources and (ii) integration
of annotated tools. We collect the sRNA information from a variety
of biological databases, such as RegulonDB, ASAP and NONCODE.
Information of sRNAs including the accessions, names, genomic
location, species, descriptions and sequences were obtained.
Furthermore, the regulator/sRNA regulations and sRNA/target
regulations were obtained from RegulonDB and NPInter (
9). In
addition to collecting data from external databases, we gather
the sRNA information by surveying literatures. Besides, RNA
secondary structures, cross-species comparisons and 37 expression
profiles of sRNAs were integrated into the database. 308 computationally
identified sRNAs (
10,
11) and 114 computationally identified
regulator/sRNA regulations and sRNA/target regulations (
12,
13)
were obtained.
Gene Expression Omnibus (GEO) (
14) is a database repository
of high-throughput gene expression data and hybridization arrays,
chips, microarrays. The expression profiles related to sRNA
were obtained and integrated. Besides, UCSC Archaeal Genome
Browser (
15), which is a popular web-based tool for quickly
displaying a requested portion of a genome at any scale, was
integrated to provide the sequence conservation of sRNAs. RNAfold
(
16) was applied to fold the RNA secondary structures of sRNAs.
Moreover, RNALogo (
17), which presents a graphical representation
of the patterns in an aligned RNA sequence family with a consensus
structure, was integrated for presenting the sRNA families.
The cross-links to other biological databases are provided for
each sRNA in the database. The integrated external data sources,
the linked external data sources and the integrated annotated
tools are listed in
Table S1, Table S2 and Table S3 (see Supplementary Materials),
respectively.
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INTERFACE
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The sRNAMap provides a variety of interfaces and graphical visualization
to present the plentiful information of sRNAs. Users can submit
keywords or sequences to search the database. For each sRNA
gene, the database provides the sequence, the genomic location,
promoter information, secondary structures, literatures, annotations,
expression profiles, sequence conservation and its transcriptional
regulatory network. Additionally, the sRNAMap has the regulator/sRNA
page and the sRNA/target page which provide the experimental
conditions and the regulator/sRNA regulations and sRNA/target
regulations.
Figure S1 shows the interface of sRNA genes in
sRNAMap.
sRNAMap also provides several browsing functions, such as the genome browser, the network browser, the expression profile browser, the computational sRNAs browser and the literature record browser (Figure S2, see Supplementary Materials).
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DISCUSSIONS
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sRNAMap is an integrated and comprehensive database comprising
plentiful information about sRNA.
Table 3 gives the comparison
of sRNAMap with other databases related to sRNA including RegulonDB,
ASAP, NONCODE, NPInter and Rfam (
18). sRNAMAp aims on the annotation
of small non-coding RNAs in microbial genomes, while Rfam mainly
aims on the collection of non-coding RNA families and a variety
of regulatory RNA structural motifs. Rfam currently collects
53 sRNA families. Our proposed sRNAMap collects 87
E. coli sRNAs
and totally 397 sRNAs from 70 species. Moreover, sRNAMap also
collects computational sRNA and supports information about RNA
secondary structures, transcriptional start sites of sRNA and
especially the expression profiles of sRNA. Consequently, we
would like to say that sRNAMap provides more plentiful and effective
information than Rfam and other databases in the aspect of sRNAs.
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AVAILABILITY
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The sRNAMap database will be continuously maintained and updated.
The database is now freely available at
http://sRNAMap.mbc.nctu.edu.tw/.
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SUPPLEMENTARY DATA
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Supplementary Data are available at NAR Online.
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FUNDING
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The National Science Council of the Republic of China (Contract
No. NSC 96-3112-E-009-002, NSC 95-2311-B-009-004-MY3 and 97-2627-B-009-007);
National Research Program for Genomic Medicine (NRPGM), Taiwan;
MOE ATU (Partial). Funding for the open access publication charge:
National Science Council of the Republic of China and MOE ATU.
Conflict of Interest statement: None declared.
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ACKNOWLEDGEMENTS
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Special thanks for financial support go to the National Research
Program for Genomic Medicine (NRPGM), Taiwan.
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ABSTRACT
INTRODUCTION
