miRNAminer: a tool for homologous microRNA gene search - PubMed (original) (raw)
Comparative Study
miRNAminer: a tool for homologous microRNA gene search
Shay Artzi et al. BMC Bioinformatics. 2008.
Abstract
Background: MicroRNAs (miRNAs), present in most metazoans, are small non-coding RNAs that control gene expression by negatively regulating translation through binding to the 3'UTR of mRNA transcripts. Previously, experimental and computational methods were used to construct miRNA gene repositories agreeing with careful submission guidelines.
Results: An algorithm we developed - miRNAminer - is used for homologous conserved miRNA gene search in several animal species. Given a search query, candidate homologs from different species are tested for their known miRNA properties, such as secondary structure, energy and alignment and conservation, in order to asses their fidelity. When applying miRNAminer on seven mammalian species we identified several hundreds of high-confidence homologous miRNAs increasing the total collection of (miRbase) miRNAs, in these species, by more than 50%. miRNAminer uses stringent criteria and exhibits high sensitivity and specificity.
Conclusion: We present - miRNAminer - the first web-server for homologous miRNA gene search in animals. miRNAminer can be used to identify conserved homolog miRNA genes and can also be used prior to depositing miRNAs in public databases. miRNAminer is available at http://pag.csail.mit.edu/mirnaminer.
Figures
Figure 1
A sample output of miRNAminer. Indicated are: search start and end times (rows 1 and 24, respectively) and the species and assembly searched (rows 2–3); whether a match (a miRNA homolog), or matches, that passed the input criteria were found (rows 4–5); information about the quality of the homolog miRNA match such as BLAST e-value, genomic location, sequence, RNA fold and energy, pairing, length and alignment with input sequence (rows 6–19). A hyperlink to the genomic locus of the miRNA homolog is also provided through Ensembl ContigView [18] or UCSC Genome Browser [43] (rows 20–23) and a copy of the users' input data (row 25).
Figure 2
Two examples of a non-miRbase registered miRNA identified using our miRNAminer web-server. (A) Human miR-764 was identified using miRbase mouse miR-764 sequence as input (and default parameters) for miRNAminer search. The output reported a homolog (presumably hsa-miR-764), which is located in the second intron of human serotonin receptor 2C (HTR2C; NM 000868). The mouse miRNA homolog is located in an intron of the same gene (HTR2C; NM 008312) suggesting an evolutionary conserved co-expression of miRNA and its host gene [27-29]. High conservation is seen in this region (mountain-like graph derived from UCSC Genome Browser 17 species multiZ alignment; [43]). Black rectangles represent exons (shorter rectangles in C are UTRs), lines are introns and dark-grey rectangles are miRNA genes. (B) RNA secondary structure of both the identified human (top) and mouse (bottom) miR-764 exhibit similar thermodynamic stability (41.8/49.9 kcal/mol, respectively) and structures (mature miRNA region is underlined). Human miR-764 homolog was also identified by Berezikov [21]. (C) Non-registered (miRbase) human miR-763 is highly conserved among vertebrate species and can potentially bind its own host gene. On top; a schematic non-scaled representation of the HMGA2 transcript (NM 003483; human miR-763 is in dark-grey; conservation plot as shown in A). Expressed Sequence Tags (ESTs; light-grey bars) are evidence for the expression of this particular genomic region. ESTs from top to bottom: BM715067 (isolated from eye-related tissue); BJ997562 (isolated from wilms tumor tissue); BU39975 (isolated from eye-related tissue); AI935081 (tissue source unknown). On the right; the potential binding site of miR-763 in HMGA2 3'UTR (nt 2–8 of the miRNA; positions 2192–2198) is conserved to human, mouse and rat.
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