Comparative analysis of structured RNAs in S. cerevisiae indicates a multitude of different functions

<p>Abstract</p> <p>Background</p> <p>Non-coding RNAs (ncRNAs) are an emerging focus for both computational analysis and experimental research, resulting in a growing number of novel, non-protein coding transcripts with often unknown functions. Whole genome screens in higher eukaryotes, for example, provided evidence for a surprisingly large number of ncRNAs. To supplement these searches, we performed a computational analysis of seven yeast species and searched for new ncRNAs and RNA motifs.</p> <p>Results</p> <p>A comparative analysis of the genomes of seven yeast species yielded roughly 2800 genomic loci that showed the hallmarks of evolutionary conserved RNA secondary structures. A total of 74% of these regions overlapped with annotated non-coding or coding genes in yeast. Coding sequences that carry predicted structured RNA elements belong to a limited number of groups with common functions, suggesting that these RNA elements are involved in post-transcriptional regulation and/or cellular localization. About 700 conserved RNA structures were found outside annotated coding sequences and known ncRNA genes. Many of these predicted elements overlapped with UTR regions of particular classes of protein coding genes. In addition, a number of RNA elements overlapped with previously characterized antisense transcripts. Transcription of about 120 predicted elements located in promoter regions and other, previously un-annotated, intergenic regions was supported by tiling array experiments, ESTs, or SAGE data.</p> <p>Conclusion</p> <p>Our computational predictions strongly suggest that yeasts harbor a substantial pool of several hundred novel ncRNAs. In addition, we describe a large number of RNA structures in coding sequences and also within antisense transcripts that were previously characterized using tiling arrays.</p

Multiple sequence alignments of partially coding nucleic acid sequences

BACKGROUND: High quality sequence alignments of RNA and DNA sequences are an important prerequisite for the comparative analysis of genomic sequence data. Nucleic acid sequences, however, exhibit a much larger sequence heterogeneity compared to their encoded protein sequences due to the redundancy of the genetic code. It is desirable, therefore, to make use of the amino acid sequence when aligning coding nucleic acid sequences. In many cases, however, only a part of the sequence of interest is translated. On the other hand, overlapping reading frames may encode multiple alternative proteins, possibly with intermittent non-coding parts. Examples are, in particular, RNA virus genomes. RESULTS: The standard scoring scheme for nucleic acid alignments can be extended to incorporate simultaneously information on translation products in one or more reading frames. Here we present a multiple alignment tool, codaln, that implements a combined nucleic acid plus amino acid scoring model for pairwise and progressive multiple alignments that allows arbitrary weighting for almost all scoring parameters. Resource requirements of codaln are comparable with those of standard tools such as ClustalW. CONCLUSION: We demonstrate the applicability of codaln to various biologically relevant types of sequences (bacteriophage Levivirus and Vertebrate Hox clusters) and show that the combination of nucleic acid and amino acid sequence information leads to improved alignments. These, in turn, increase the performance of analysis tools that depend strictly on good input alignments such as methods for detecting conserved RNA secondary structure elements

Interleukin-6-dependent survival of multiple myeloma cells involves the Stat3-mediated induction of micro-RNA-21 through a highly conserved enhancer

Signal transducer and activator of transcription 3 (Stat3) is implicated in the pathogenesis of many malignancies and essential for IL-6–dependent survival and growth of multiple myeloma cells. Here, we demonstrate that the gene encoding oncogenic microRNA-21 (miR-21) is controlled by an upstream enhancer containing 2 Stat3 binding sites strictly conserved since the first observed evolutionary appearance of miR-21 and Stat3. MiR-21 induction by IL-6 was strictly Stat3 dependent. Ectopically raising miR-21 expression in myeloma cells in the absence of IL-6 significantly reduced their apoptosis levels. These data provide strong evidence that miR-21 induction contributes to the oncogenic potential of Stat3

Intramolecular Domain Movements of Free and Bound pMHC and TCR Proteins: A Molecular Dynamics Simulation Study

The interaction of antigenic peptides (p) and major histocompatibility complexes (pMHC) with T-cell receptors (TCR) is one of the most important steps during the immune response. Here we present a molecular dynamics simulation study of bound and unbound TCR and pMHC proteins of the LC13-HLA-B*44:05-pEEYLQAFTY complex to monitor differences in relative orientations and movements of domains between bound and unbound states of TCR-pMHC. We generated local coordinate systems for MHC &alpha;1- and MHC &alpha;2-helices and the variable T-cell receptor regions TCR V&alpha; and TCR V&beta; and monitored changes in the distances and mutual orientations of these domains. In comparison to unbound states, we found decreased inter-domain movements in the simulations of bound states. Moreover, increased conformational flexibility was observed for the MHC &alpha;2-helix, the peptide, and for the complementary determining regions of the TCR in TCR-unbound states as compared to TCR-bound states

Multiple sequence alignments of partially coding nucleic acid sequences

High quality sequence alignments of RNA and DNA sequences are an important prerequisite for the comparative analysis of genomic sequence data. Nucleic acid sequences, however, exhibit a much larger sequence heterogeneity compared to their encoded protein sequences due to the redundancy of the genetic code. It is desirable, therefore, to make use of the amino acid sequence when aligning coding nucleic acid sequences. In many cases, however, only a part of the sequence of interest is translated. On the other hand, overlapping reading frames may encode multiple alternative proteins, possibly with intermittent non-coding parts. Examples are, in particular, RNA virus genomes

Centrala faktorer vid extern chefsrekrytering

En organisation kan anlita en extern rekryteringskonsult, att ansvara för rekryteringsprocessen när en ny medarbetare ska rekryteras. Det sker ofta i samband med chefsrekrytering. Syftet med studien var att öka förståelsen för centrala faktorer vid extern chefsrekrytering och vilka faktorer hos kandidaten som externa rekryteringskonsulter bedömer som viktiga för att kandidaten kan komma att presenteras för kunden. Studien har kommit fram till att kandidatens utbildning, yrkeserfarenhet och personliga egenskaper ska stämma in på kravprofil och rollbeskrivningen för tjänsten. Referenser och psykologiska test och personlighetsformulär används för att bekräfta kandidatens egna uppgifter och rekryteringskonsultens helhetsbedömning. Det används också som underlag vid intervjuer med kandidaten. Resultatet i studien kan kopplas till tidigare studier och litteratur på ämnesområdet. Studien är användbar för psykologiska studier inom ämnesområdet chefsrekrytering, för den som är intresserade av hur extern chefsrekrytering fungerar och för den som kan tänka sig en framtid inom rekryteringsbranschen

Correlation of 'predicted RNA structures' with UTR-regions and TF-binding sites

<p><b>Copyright information:</b></p><p>Taken from "Comparative analysis of structured RNAs in indicates a multitude of different functions"</p><p>http://www.biomedcentral.com/1741-7007/5/25</p><p>BMC Biology 2007;5():25-25.</p><p>Published online 18 Jun 2007</p><p>PMCID:PMC1914338.</p><p></p> (a) Number of 'predicted RNA structures' in intervals of increasing length adjacent to coding sequences. (b) Number of 'predicted RNA structures' overlapping with transcription factor binding sites taken from [18]

Known RNA genes in the yeast genome, covered by predicted RNA structures

<p><b>Copyright information:</b></p><p>Taken from "Comparative analysis of structured RNAs in indicates a multitude of different functions"</p><p>http://www.biomedcentral.com/1741-7007/5/25</p><p>BMC Biology 2007;5():25-25.</p><p>Published online 18 Jun 2007</p><p>PMCID:PMC1914338.</p><p></p> The annotation was taken from the Genome Database. Structured elements with reported values larger than 0.5 (left) and 0.9 (right) are shown

Examples of predicted ncRNAs: genomic context, tiling array pattern and predicted consensus structure

<p><b>Copyright information:</b></p><p>Taken from "Comparative analysis of structured RNAs in indicates a multitude of different functions"</p><p>http://www.biomedcentral.com/1741-7007/5/25</p><p>BMC Biology 2007;5():25-25.</p><p>Published online 18 Jun 2007</p><p>PMCID:PMC1914338.</p><p></p> The color scheme used for coloring the RNA structures and the mountain plots representation is the same as in Figure 2. (a) and (b) Intergenic region with predicted RNA overlaps with transcripts described by David et al [9]. Note, that in (b) the sequence for sacKud.contig1979/20479-20583 is truncated (a stretch of seven gaps in the 3' end of the stem, which is not compensated by the deletions in the 5' part of the stem), which probably renders an unusable RNA due to an altered secondary structure. (c) Intergenic region with predicted RNA overlaps with promoter associated transcript described by Samanta et al [7]. (d) Predicted H/ACA snoRNA, overlapping with transcripts described by both David et al [7] and Davis et al [8]

Interleukin-6-dependent survival of multiple myeloma cells involves the Stat3-mediated induction of micro-RNA-21 through a highly conserved enhancer

Signal transducer and activator of transcription 3 (Stat3) is implicated in the pathogenesis of many malignancies and essential for IL-6–dependent survival and growth of multiple myeloma cells. Here, we demonstrate that the gene encoding oncogenic microRNA-21 (miR-21) is controlled by an upstream enhancer containing 2 Stat3 binding sites strictly conserved since the first observed evolutionary appearance of miR-21 and Stat3. MiR-21 induction by IL-6 was strictly Stat3 dependent. Ectopically raising miR-21 expression in myeloma cells in the absence of IL-6 significantly reduced their apoptosis levels. These data provide strong evidence that miR-21 induction contributes to the oncogenic potential of Stat3