It has been known that circular RNAs are widely expressed in human tissues and cells, and play important regulatory roles in physiological or pathological processes. However, there is lack of comprehensively annotated human circular RNAs database. In this study we established a circRNA database, named as circRNADb, containing 32,914 human exonic circRNAs carefully selected from diversified sources. The detailed information of the circRNA, including genomic information, exon splicing, genome sequence, internal ribosome entry site (IRES), open reading frame (ORF) and references were provided in circRNADb. In addition, circRNAs were found to be able to encode proteins, which have not been reported in any species. 16328 circRNAs were annotated to have ORF longer than 100 amino acids, of which 7170 have IRES elements. 46 circRNAs from 37 genes were found to have their corresponding proteins expressed according mass spectrometry. The database provides the function of data search, browse, download, submit and feedback for the user to study particular circular RNA of interest and update the database continually. circRNADb will be built to be a biological information platform for circRNA molecules and related biological functions in the future. The database can be freely available through the web server at http://reprod.njmu.edu.cn/circrnadb.

Circular RNA (circRNA) is one type of noncoding RNA that forms a covalently closed continuous loop. Similar to long noncoding RNA (lncRNA), circRNA can act as microRNA (miRNA) ‘sponges’ to regulate gene expression, and its abnormal expression is related to diseases such as atherosclerosis, nervous system disorders and cancer. So far, there have been no systematic studies on circRNA abundance and expression profiles in human adult and fetal tissues. We explored circRNA expression profiles using RNA-seq data for six adult and fetal normal tissues (colon, heart, kidney, liver, lung, and stomach) and four gland normal tissues (adrenal gland, mammary gland, pancreas, and thyroid gland). A total of 8120, 25,933 and 14,433 circRNAs were detected by at least two supporting junction reads in adult, fetal and gland tissues, respectively. Among them, 3092, 14,241 and 6879 circRNAs were novel when compared to the published results. In each adult tissue type, we found at least 1000 circRNAs, among which 36.97–50.04% were tissue-specific. We reported 33 circRNAs that were ubiquitously expressed in all the adult tissues we examined. To further explore the potential “housekeeping” function of these circRNAs, we constructed a circRNA-miRNA-mRNA regulatory network containing 17 circRNAs, 22 miRNAs and 90 mRNAs. Furthermore, we found that both the abundance and the relative expression level of circRNAs were higher in fetal tissue than adult tissue. The number of circRNAs in gland tissues, especially in mammary gland (9665 circRNA candidates), was higher than that of other adult tissues (1160–3777). We systematically investigated circRNA expression in a variety of human adult and fetal tissues. Our observation of different expression level of circRNAs in adult and fetal tissues suggested that circRNAs might play their role in a tissue-specific and development-specific fashion. Analysis of circRNA-miRNA-mRNA network provided potential targets of circRNAs. High expression level of circRNAs in mammary gland might be attributed to the rich innervation.

Long intergenic non-coding RNAs (lincRNAs) are emerging as a novel class of non-coding RNAs and potent gene regulators. High-throughput RNA-sequencing combined with de novo assembly promises quantity discovery of novel transcripts. However, the identification of lincRNAs from thousands of assembled transcripts is still challenging due to the difficulties of separating them from protein coding transcripts (PCTs). We have implemented iSeeRNA, a support vector machine (SVM)-based classifier for the identification of lincRNAs. iSeeRNA shows better performance compared to other software. A public available webserver for iSeeRNA is also provided for small size dataset. iSeeRNA demonstrates high prediction accuracy and runs several magnitudes faster than other similar programs. It can be integrated into the transcriptome data analysis pipelines or run as a web server, thus offering a valuable tool for lincRNA study.

Internal ribosome entry sites (IRESs) are functional RNA elements that can directly recruit ribosomes to an internal position of the mRNA in a cap-independent manner to initiate translation. Recently, IRES elements have attracted much attention for their critical roles in various processes including translation initiation of a new type of RNA, circular RNA (circRNA), with no 5′ cap to support classical cap-dependent translation. Thus, an integrative data resource of IRES elements with experimental evidence will be useful for further studies. In this study, we present IRESbase, a comprehensive database of IRESs, by curating the experimentally validated functional minimal IRES elements from literature and annotating their host linear and circular RNAs. The current version of IRESbase contains 1328 IRESs, including 774 eukaryotic IRESs and 554 viral IRESs from 11 eukaryotic organisms and 198 viruses, respectively. As IRESbase collects only IRES of minimal length with functional evidence, the median length of IRESs in IRESbase is 174 nucleotides. By mapping IRESs to human circRNAs and long non-coding RNAs (lncRNAs), 2191 circRNAs and 168 lncRNAs were found to contain at least one entire or partial IRES sequence. IRESbase is available at http://reprod.njmu.edu.cn/cgi-bin/iresbase/index.php.

Protein ubiquitination is one of the important post-translational modifications by attaching ubiquitin to specific lysine (K) residues in target proteins, and plays important regulatory roles in many cell processes. Recent studies indicated that abnormal protein ubiquitination have been implicated in many diseases by degradation of many key regulatory proteins including tumor suppressor, oncoprotein, and cell cycle regulator. The detailed information of protein ubiquitination sites is useful for scientists to investigate the mechanism of many cell activities and related diseases. In this study we established mUbiSida for mammalian Ubiquitination Site Database, which provides a scientific community with a comprehensive, freely and high-quality accessible resource of mammalian protein ubiquitination sites. In mUbiSida, we deposited about 35,494 experimentally validated ubiquitinated proteins with 110,976 ubiquitination sites from five species. The mUbiSiDa can also provide blast function to predict novel protein ubiquitination sites in other species by blast the query sequence in the deposit sequences in mUbiSiDa. The mUbiSiDa was designed to be a widely used tool for biologists and biomedical researchers with a user-friendly interface, and facilitate the further research of protein ubiquitination, biological networks and functional proteomics. The mUbiSiDa database is freely available at http://reprod.njmu.edu.cn/mUbiSiDa.