No abstract

The 5′ and 3′ untranslated regions of eukaryotic mRNAs (UTRs) play crucial roles in the post-transcriptional regulation of gene expression through the modulation of nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization and message stability. UTRdb is a curated database of 5′ and 3′ untranslated sequences of eukaryotic mRNAs, derived from several sources of primary data. Experimentally validated functional motifs are annotated and also collated as the UTRsite database where more specific information on the functional motifs and cross-links to interacting regulatory protein are provided. In the current update, the UTR entries have been organized in a gene-centric structure to better visualize and retrieve 5′ and 3′UTR variants generated by alternative initiation and termination of transcription and alternative splicing. Experimentally validated miRNA targets and conserved sequence elements are also annotated. The integration of UTRdb with genomic data has allowed the implementation of an efficient annotation system and a powerful retrieval resource for the selection and extraction of specific UTR subsets. All internet resources implemented for retrieval and functional analysis of 5′ and 3′ untranslated regions of eukaryotic mRNAs are accessible at http://utrdb.ba.itb.cnr.it/.

The 5 0 and 3 0 untranslated regions of eukaryotic mRNAs play crucial roles in the post-transcriptional regulation of gene expression through the modulation of nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization and message stability. UTRdb is a curated database of 5 0 and 3 0 untranslated sequences of eukaryotic mRNAs, derived from several sources of primary data. Experimentally validated functional motifs are annotated (and also collated as the UTRsite database) and cross-links to genomic and protein data are provided.

The 5' and 3' untranslated regions of eukaryotic mRNAs may play a crucial role in the regulation of gene expression controlling mRNA localization, stability and translational efficiency. For this reason we developed UTRdb, a specialized database of 5' and 3' untranslated sequences of eukaryotic mRNAs cleaned from redundancy. UTRdb entries are enriched with specialized information not present in the primary databases including the presence of nucleotide sequence patterns already demonstrated by experimental analysis to have some functional role. All these patterns have been collected in the UTRsite database so that it is possible to search any input sequence for the presence of annotated functional motifs. Furthermore, UTRdb entries have been annotated for the presence of repetitive elements. All internet resources implemented for retrieval and functional analysis of 5' and 3' untranslated regions of eukaryotic mRNAs are accessible at http://bigarea.area.ba.cnr.it:8000/EmbIT/UTRH ome/

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease. While genetics and other factors contribute to ALS pathogenesis, critical knowledge is still missing and validated biomarkers for monitoring the disease activity have not yet been identified. To address those aspects we carried out this study with the primary aim of identifying possible miRNAs/mRNAs dysregulation associated with the sporadic form of the disease (sALS). Additionally, we explored miRNAs as modulating factors of the observed clinical features. Study included 56 sALS and 20 healthy controls (HCs). We analyzed the peripheral blood samples of sALS patients and HCs with a high-throughput next-generation sequencing followed by an integrated bioinformatics/biostatistics analysis. Results showed that 38 miRNAs (let-7a-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-103a-3p, miR-106b-3p, miR-128-3p, miR-130a-3p, miR-130b-3p, miR-144-5p, miR-148a-3p, miR-148b-3p, miR-15a-5p, miR-15b-5p, miR-151a-5p, miR-151b, miR-16-5p, miR-182-5p, miR-183-5p, miR-186-5p, miR-22-3p, miR-221-3p, miR-223-3p, miR-23a-3p, miR-26a-5p, miR-26b-5p, miR-27b-3p, miR-28-3p, miR-30b-5p, miR-30c-5p, miR-342-3p, miR-425-5p, miR-451a, miR-532-5p, miR-550a-3p, miR-584-5p, miR-93-5p) were significantly downregulated in sALS. We also found that different miRNAs profiles characterized the bulbar/spinal onset and the progression rate. This observation supports the hypothesis that miRNAs may impact the phenotypic expression of the disease. Genes known to be associated with ALS (e.g., PARK7, C9orf72, ALS2, MATR3, SPG11, ATXN2) were confirmed to be dysregulated in our study. We also identified other potential candidate genes like LGALS3 (implicated in neuroinflammation) and PRKCD (activated in mitochondrial-induced apoptosis). Some of the downregulated genes are involved in molecular bindings to ions (i.e., metals, zinc, magnesium) and in ions-related functions. The genes that we found upregulated were involved in the immune response, oxidation–reduction, and apoptosis. These findings may have important implication for the monitoring, e.g., of sALS progression and therefore represent a significant advance in the elucidation of the disease’s underlying molecular mechanisms. The extensive multidisciplinary approach we applied in this study was critically important for its success, especially in complex disorders such as sALS, wherein access to genetic background is a major limitation.