Thousands of long intergenic noncoding RNAs (lincRNAs) are encoded by the mammalian genome, which were reported to have multiple biological functions as transcriptional activators acting in cis 1 or trans 2, transcriptional repressors 3,4 or miRNAs decoys 5,6. However, the function of most lincRNAs has not yet been identified in vivo. Here, we demonstrate a role for linc-MYH, a novel long intergenic noncoding RNA, in adult fast-type myofibre specialization. Skeletal myofibre fast and slow phenotypes are established through differential expression of numerous fibre-specific genes7. We show linc-MYH and the fast MYH genes share a common enhancer located in the fast MYH genes locus and regulated by the Six1 homeoproteins. Muscle-specific Six1 mutant mice show increased expression of slow-type genes, and downregulation of linc-MYH and fast-type genes. linc-MYH function revealed by in vivo knockdown and wide transcriptomic analysis, is in fine to prevent expression of genes ensuring slow muscle contractile properties, and to increase fast-type muscle gene expression in fast-type myofibres. Thus, formation of efficient fast sarcomeric units and appropriate Ca++ cycling and excitation/contraction/relaxation coupling in fast- myofibres is achieved through the coordiante control of fast MYHs and linc-MYH expression by a Six bound enhancer.
Six homeoproteins and a Iinc-RNA at the fast MYH locus lock fast myofiber terminal phenotype.
Age, Specimen part
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A systems immunology approach identifies the collective impact of 5 miRs in Th2 inflammation.
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View SamplesAllergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including miRNAs, are pivotal in maintaining immune-homeostasis. Since an altered expression of various miRNAs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRNAs control mechanisms ensuring Th2 stability and maintenance in the lung. We isolated murine CD4+ Th2 cells from allergic inflamed lungs and profiled gene and microRNA expression.
A systems immunology approach identifies the collective impact of 5 miRs in Th2 inflammation.
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View SamplesTerminal differentiation of epidermal cells in Drosophila embryos requires the activity of a transcription factor. Svb is necessary and sufficient to induce this process. pri is a regulator of Svb activity, converting it from a repressor into an activator. To characterize the downstream Svb and pri effectors in cell morphogenesis, we performed microarrays in wt, svb -/- (no gene) and pri -/- (svb repressor) mutant conditions.
Genome-wide analyses of Shavenbaby target genes reveals distinct features of enhancer organization.
Specimen part
View SamplesWe measured transcriptional changes in four strains P2, rpoD3, rpoA14, and rpoA27 - in an effort to understand mechanisms by which L-tyrosine production is positively influenced by the presence of mutant rpoA- and rpoD-encoded transcriptional components.
Rational, combinatorial, and genomic approaches for engineering L-tyrosine production in Escherichia coli.
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View Samplesthe nuclear pore complex (NPC) is emerging as an important mediator of cellular processes beyond molecule transport, including control of gene expression, replication and DNA repair.
The Nup84 complex coordinates the DNA damage response to warrant genome integrity.
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View SamplesAnalysis of the transcriptional profiles of mRNA and microRNA in Rasless fibroblasts. 4-Hydroxy-tamoxifen (4-OHT) treatment triggers removal of K-Ras expression in [H-Ras-/-;N-Ras-/-;K-Raslox/lox;RERTert/ert ] mouse fibroblasts (named K-Raslox) generating Rasless MEFs which are unable to proliferate, but recover proliferative ability after ectopic expression of constitutively active downstream kinases such as BRAF and MEK1.
Reversible, interrelated mRNA and miRNA expression patterns in the transcriptome of Rasless fibroblasts: functional and mechanistic implications.
Specimen part, Cell line, Treatment
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A genome-wide function of THSC/TREX-2 at active genes prevents transcription-replication collisions.
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View SamplesTranscription is a major obstacle for replication fork progression and a cause of genome instability. Such instability increases in mutants with a suboptimal assembly of the nascent messenger ribonucleo-protein particle (mRNP), as THO/TREX and the NPC-associated THSC/TREX-2 complex.
A genome-wide function of THSC/TREX-2 at active genes prevents transcription-replication collisions.
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Excess of Yra1 RNA-Binding Factor Causes Transcription-Dependent Genome Instability, Replication Impairment and Telomere Shortening.
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