Background Functional RNA molecules participate in numerous biological processes, ranging from gene regulation to protein synthesis. Analysis of functional RNA motifs and elements in RNA sequences can obtain useful information for deciphering RNA regulatory mechanisms. Our previous work, RegRNA, is widely used in the identification of regulatory motifs, and this work extends it by incorporating more comprehensive and updated data sources and analytical approaches into a new platform. Methods and results An integrated web-based system, RegRNA 2.0, has been developed for comprehensively identifying the functional RNA motifs and sites in an input RNA sequence. Numerous data sources and analytical approaches are integrated, and several types of functional RNA motifs and sites can be identified by RegRNA 2.0: (i) splicing donor/acceptor sites; (ii) splicing regulatory motifs; (iii) polyadenylation sites; (iv) ribosome binding sites; (v) rho-independent terminator; (vi) motifs in mRNA 5'-untranslated region (5'UTR) and 3'UTR; (vii) AU-rich elements; (viii) C-to-U editing sites; (ix) riboswitches; (x) RNA cis-regulatory elements; (xi) transcriptional regulatory motifs; (xii) user-defined motifs; (xiii) similar functional RNA sequences; (xiv) microRNA target sites; (xv) non-coding RNA hybridization sites; (xvi) long stems; (xvii) open reading frames; (xviii) related information of an RNA sequence. User can submit an RNA sequence and obtain the predictive results through RegRNA 2.0 web page. Conclusions RegRNA 2.0 is an easy to use web server for identifying regulatory RNA motifs and functional sites. Through its integrated user-friendly interface, user is capable of using various analytical approaches and observing results with graphical visualization conveniently. RegRNA 2.0 is now available at http://regrna2.mbc.nctu.edu.tw.

Gastric cancer (GC) is the second leading cause of global cancer mortality. Most GC patients are diagnosed with advanced-stage disease and show extremely poor prognosis. All of the GC research has a common interest to search for the specific and sensitive biomarkers for early diagnosis of GC. Number of microRNAs play important role in GC. We carried out a systematic review of published miRNA profiling studies that compared the miRNA expression profiles between GC tissues and paired noncancerous gastric tissue. A vote-counting strategy was followed with the collection of information like total number of studies reporting differential expression of miRNA, total number of tissue samples used in the studies, direction of differential expression and fold change. A total of 352 differentially expressed microRNAs were reported in the 14 microRNA expression profiling studies that compared GC tissues with normal tissues with 120 microRNAs reported at least in two studies. In the group of consistently reported microRNAs, miR-21 was reported upregulated in 10 studies followed by miR-25, miR-92, and miR-223 upregulated in eight studies. MiR-375 and miR-148a were found downregulated in six and five studies, respectively, followed by miR-638 in four studies. MiR-107 and miR-103 were reported in nine and eight studies, respectively, but their expression were inconsistent. From this study, the most consistently reported upregulated microRNA was found to be miR-21. This systematic review study of human GC microRNA expression profiling studies would provide information on microRNAs with potential role as the biomarkers in gastric cancer.

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/.

Background Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall [e.g., endothelial cells (ECs)] as well as circulating and resident immunogenic cells (e.g., monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of sterol regulatory element binding protein 2 (SREBP2), 25-hydroxycholesterol (25-HC) and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages. Methods Bioinformatic analyses were used to investigate RNA-seq data to identify cholesterol oxidation and efflux genes regulated by KLF4. In vitro experiments involving cultured ECs and macrophages and in vivo methods involving mice with Ch25h ablation were then used to explore the atheroprotective role of KLF4-Ch25h/LXR. Results Vasoprotective stimuli increased the expression of Ch25h and LXR via krüppel-like factor 4 (KLF4). The KLF4-Ch25h/LXR homeostatic axis functions through suppressing inflammation, evidenced by the reduction of inflammasome activity in ECs and the promotion of M1 to M2 phenotypic transition in macrophages. The increased atherosclerosis in ApoE−/−/Ch25h−/− mice further demonstrates the beneficial role of the KLF4-Ch25h/LXR axis in vascular function and disease. Conclusions KLF4 transactivates Ch25h and LXR thereby promoting the synergistic effects between ECs and macrophages to protect against atherosclerosis susceptibility.

CPEB3 is a sequence-specific RNA-binding protein and represses translation of its target mRNAs in neurons. Here, we have identified a novel function of CPEB3 as to interact with Stat5b and inhibit its transcription activity in the nucleus without disrupting dimerization, DNA binding and nuclear localization of Stat5b. Moreover, CPEB3 is a nucleocytoplasm-shuttling protein with predominant residence in the cytoplasm; whereas activation of NMDA receptors accumulates CPEB3 in the nucleus. Using the knockdown approach, we have found the receptor tyrosine kinase, EGFR, is a target gene transcriptionally activated by Stat5b and downregulated by CPEB3 in neurons. The increased EGFR expression in CPEB3 knockdown neurons, when stimulated with EGF, alters the kinetics of downstream signaling. Taken together, CPEB3 has a novel function in the nucleus as to suppress Stat5b-dependent EGFR gene transcription. Consequently, EGFR signaling is negatively regulated by CPEB3 in neurons.