micrornas ( mirnas ) are small ( 2123 nt ) non - coding rnas that are important regulators of gene expression .
they act by base pairing with partially complementary sites in the mrna of their targets , and either inhibit translation into protein or decrease the stability of the transcript ( 1,2 ) .
the number of currently known mirnas in mammalian systems has risen dramatically in the last year , and predictions about their total number in humans amount up to 1000 ( 3 ) .
mirnas are transcribed as long primary transcripts ( pri - mirnas ) , some of them being polycistronic , which are processed in the cell nucleus by an enzyme called drosha , yielding precursor mirnas ( pre - mirnas ) that exhibit a characteristic stem  loop sequence .
these are exported into the cytosol where mature mirnas are generated by the rnase iii - type enzyme dicer , producing a small double - stranded rna from which one strand ( called mirna * ) is quickly degraded , releasing the small single - stranded mirna ( 4 ) .
translational inhibition , which seems to be the major mode of action in animals , is performed by a riboprotein complex called rna - induced silencing complex ( risc ) consisting of the mirna and proteins of the argonaute family ( 5,6 ) .
mirnas are involved in several cellular processes , including cellular differentiation ( 7,8 ) , organism development ( 9,10 ) and apoptosis ( 11,12 ) . while all of these are conserved in metazoans
, the number of conserved mirnas between mammals suggests that there are additional functions only found in vertebrates ( 13 ) , e.g. controlling hematopoietic differentiation ( 14 ) .
recent studies provide growing evidence for the involvement of mirnas in cancerogenesis ( 1518 ) .
the advantages of argonaute over current databases on mirnas are as follows : it has information on ( i ) origin of a mirna , i.e. in which host gene it is encoded , ( ii ) its expression in different tissues and its known or proposed function , ( iii ) its potential target genes including gene ontology annotation as well as ( iv ) on mirna families and proteins known to be involved in mirna processing .
the first release of argonaute contains 839 mirnas from human , mouse and rat . in summary , argonaute is a comprehensive database for mammalian mirnas collecting all available latest information about mirna expression , pre - mirna sequence and length of the stem  loop region , function and potential target genes , and is thus providing a valuable platform for quick and efficient access to all important information on the fast growing field of mirna research . through a user - friendly web interface at ,
as main sources for mirnas and corresponding annotation , we used the mirbase sequence database ( 19 ) .
we further checked noncode ( 20 ) and rnadb ( 21 ) for mirnas that were not contained in mirbase::sequences like hsa - mir-350 and hsa - mir-196 - 4 .
these have been reported in literature ( 22 ) , but the only information given there is that they are contained within intron 6 of ensg00000143702 .
owing to the lack of other information , we also decided not to include them in argonaute .
for individual mirnas with direct support in the literature , the details ( sequence , accession number , chromosomal location , etc . )
additional annotation , especially on confirmed or predicted targets of mirnas and on tissue specificity of expression , was entered manually based on primary literature .
literature scanning is done on a regular basis using my ncbi ( cubby ) in order to keep the contents of the database up - to - date .
a list of studies used for the current version of argonaute is reported in supplementary data ( supplementary table 1 ) .
information on mirnas and their targets is contained in different objects in order to be able to map the many - to - many relationships correctly .
for each mirna  target relation , individual reference to the literature is reported which is kept in a separate table to minimize redundancy .
possible queries include exact or wildcard search for an mirna name , batch retrieval based on a text file with mirna names and browsing the entire contents of the database .
a selection panel allows to tailor information retrieval by selecting or deselecting fields to be displayed in the output .
results of queries are presented in two different tables ( figure 1 ) , one on the mirnas and one on the targets ( provided that target information has been selected for display ) .
if the box  annotation for targets is unchecked , all predicted targets for a given mirna are presented in one row of the result table , together with all references .
if it is checked , there is one row per target gene , including the reference that reported the mirna 
target relationship , so it can be tracked where the evidence on the relationship has come from .
target gene identifiers are linked to ensembl to get information on the transcript assumed to be regulated by a certain mirna . the result field 
origin is linked to a third table ( figure 1 , inset ) providing comprehensive results on the gene the mirna is contained in ( many mirnas are hosted in introns of protein - coding genes ) .
additionally , a detailed list of proteins involved in mirna processing can also be obtained from the homepage .
in order to facilitate the characterization of target genes we developed an information retrieval system mainly based on several ncbi sources as well as unigene , swiss - prot and ensembl .
this allows us to perform a comprehensive search for each target gene by clicking on the gene name ( figure 2 ) .
the major advantage of our interface is that it generates an automated pubmed search using all synonyms of the individual gene ( figure 2 , inset ) .
this search can be tailored to an organ - specific search or a search for transgenes / knock - outs .
furthermore , information on the availability of the target gene on affymetrix chips is given .
the system is implemented as a php - based web interface to an mysql database .
it is capable of generating automatic search strings for the target gene in pubmed using several criteria .
it is possible to save the results of the search as an excel table for later use .
furthermore , the system is able to process a list of genes , which is very convenient when analyzing results of microarray experiments or any experiments yielding a group of related genes .
currently , argonaute hosts information on 839 mammalian mirnas from human , mouse and rat , and reports 312 mirna  target relationships .
we continue to add further information as reported in primary literature and synchronize with mirbase::sequence db ( microrna registry ) every 4 months .
we are currently developing an interface for sequence - based search that allows to find potential target sites for mirnas in the query sequence based on established mirna target - prediction algorithms .
the upper table provides comprehensive information on the mature mirna and its precursor , the middle table has information on predicted targets of hsa - mir-328 .
the inset shows additional information on the origin of this mirna , i.e. the gene it is encoded in .
the table provides comprehensive information on the gene , including affymetrix probe set ids , cross - references to other databases , synonyms and textual summary information .
the links to pubmed search by all synonyms of the gene , either alone ( inset ) or in combination with  ( transgen * or knockout or knock - out ) and ( animals[mh ] or animal [ mh]) to find reports on genetically modified organisms where this gene is altered or deleted .
 micrornas ( mirnas ) constitute a recently discovered class of small non - coding rnas that regulate expression of target genes either by decreasing the stability of the target mrna or by translational inhibition . 
 they are involved in diverse processes , including cellular differentiation , proliferation and apoptosis . 
 recent evidence also suggests their importance for cancerogenesis . by 
 far the most important model systems in cancer research are mammalian organisms . 
 thus , we decided to compile comprehensive information on mammalian mirnas , their origin and regulated target genes in an exhaustive , curated database called argonaute ( ) . 
 argonaute collects latest information from both literature and other databases . 
 in contrast to current databases on mirnas like mirbase::sequences , noncode or rnadb , argonaute hosts additional information on the origin of an mirna , i.e. in which host gene it is encoded , its expression in different tissues and its known or proposed function , its potential target genes including gene ontology annotation , as well as mirna families and proteins known to be involved in mirna processing . 
 additionally , target genes are linked to an information retrieval system that provides comprehensive information from sequence databases and a simultaneous search of medline with all synonyms of a given gene . 
 the web interface allows the user to get information for a single or multiple mirnas , either selected or uploaded through a text file . 
 argonaute currently has information on 839 mirnas from human , mouse and rat . 
INTRODUCTION
DATABASE IMPLEMENTATION AND DESIGN
DATABASE ACCESS AND INTERFACE
TARGET GENE INFORMATION RETRIEVAL SYSTEM
CURRENT STATUS AND FUTURE DEVELOPMENTS
SUPPLEMENTARY DATA
Supplementary Material
Figures and Tables