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Aims 3′ untranslated region (3′ UTR) of mRNA is more conserved than other non-coding sequences in vertebrate genomes, and its sequence space has substantially expanded during the evolution of higher organisms, which substantiates their significance in biological regulation. However, the independent role of 3′ UTR in cardiovascular disease was largely unknown. Methods and results Using bioinformatics, RNA fluorescent in situ hybridization and quantitative real-time polymerase chain reaction, we found that 3′ UTR and coding sequence regions of Ckip-1 mRNA exhibited diverse expression and localization in cardiomyocytes. We generated cardiac-specific Ckip-1 3′ UTR overexpression mice under wild type and casein kinase 2 interacting protein-1 (CKIP-1) knockout background. Cardiac remodelling was assessed by histological, echocardiography, and molecular analyses at 4 weeks after transverse aortic constriction (TAC) surgery. The results showed that cardiac Ckip-1 3′ UTR significantly inhibited TAC-induced cardiac hypertrophy independent of CKIP-1 protein. To determine the mechanism of Ckip-1 3′ UTR in cardiac hypertrophy, we performed transcriptome and metabolomics analyses, RNA immunoprecipitation, biotin-based RNA pull-down, and reporter gene assays. We found that Ckip-1 3′ UTR promoted fatty acid metabolism through AMPK–PPARα–CPT1b axis, leading to its protection against pathological cardiac hypertrophy. Moreover, Ckip-1 3′ UTR RNA therapy using adeno-associated virus obviously alleviates cardiac hypertrophy and improves heart function. Conclusions These findings disclose that Ckip-1 3′ UTR inhibits cardiac hypertrophy independently of its cognate protein. Ckip-1 3′ UTR is an effective RNA-based therapy tool for treating cardiac hypertrophy and heart failure. [ABSTRACT FROM AUTHOR]

Objective Bone loss is common in AS, and miR-214 plays an important role in regulating bone formation. The aim of this study was to investigate the effect of miR-214, the production of which is stimulated by IL-17A, on bone loss in AS. Methods Peripheral blood was obtained from 32 patients with AS and 24 healthy controls. Levels of IL-17A, soluble RANK ligand (RANKL) and osteoprotegerin in serum were evaluated by ELISA, and the relative level of miR-214 in serum was detected by real-time quantitative PCR. In addition, we assessed the relationship between levels of miR-214, IL-17A and bone loss in primary murine osteoblasts and mouse bone marrow cells. Results The expression of RANKL and miR-214 in osteoblasts was increased following stimulation by IL-17A, and osteoblasts stimulated by IL-17A promoted the expression of miR-214 in osteoclasts and the activity of osteoclasts. We showed that osteoblast-derived miR-214 could be transferred to osteoclasts and could then regulate their activity. The levels of IL-17A and miR-214 were much higher in the serum of patients with AS than in that of healthy controls, and the relative level of miR-214 was positively correlated with the level of IL-17A in the serum and synovial fluid of the patients with AS, not healthy controls. The level of miR-214 in the serum of AS patients has potential diagnostic value. Conclusion The production of miR-214 in osteoblasts is stimulated by IL-17A. It is an important inhibitor of bone formation in AS, and the serum level of miR-214 might be of potential diagnostic value for AS. [ABSTRACT FROM AUTHOR]

Motivation: Sequence alignment is one of the most popular tools of modern biology. NCBI's PSI-BLAST utilizes iterative model building in order to better detect distant homologs with greater sensitivity than non-iterative BLAST. However, PSI-BLAST's performance is limited by the fact that it relies on deterministic alignments. Using a semi-probabilistic alignment scheme such as Hybrid alignment should allow for better informed model building and improved identification of homologous sequences, particularly remote homologs.Results: We have built a new version of the tool in which the Smith-Waterman alignment algorithm core is replaced by the hybrid alignment algorithm. The favorable statistical properties of the hybrid algorithm allow the introduction of position-specific gap penalties in Hybrid PSI-BLAST. This improves the position-specific modeling of protein families and results in an overall improvement of performance.Availability: Source code is freely available for download at http://bioserv.mps.ohio-state.edu/HybridPSI, implemented in C and supported on linux.Contact: bundschuh@mps.ohio-state.eduSupplementary information:Supplementary data are available at Bioinformatics online. [ABSTRACT FROM PUBLISHER]