Motivation: Developing competency in the broad area of bioinformatics is challenging globally, owing to the breadth of the field and the diversity of its audiences for education and training. Course design can be facilitated by the use of a competency framework-a set of competency requirements that define the knowledge, skills and attitudes needed by individuals in (or aspiring to be in) a particular profession or role. These competency requirements can help to define curricula as they can inform both the content and level to which competency needs to be developed.
View Article and Find Full Text PDFScience, technology, engineering, mathematics, and medicine (STEMM) fields change rapidly and are increasingly interdisciplinary. Commonly, STEMM practitioners use short-format training (SFT) such as workshops and short courses for upskilling and reskilling, but unaddressed challenges limit SFT's effectiveness and inclusiveness. Education researchers, students in SFT courses, and organizations have called for research and strategies that can strengthen SFT in terms of effectiveness, inclusiveness, and accessibility across multiple dimensions.
View Article and Find Full Text PDFCircular RNAs are important for many cellular processes but their mechanisms of action remain poorly understood. Here, we map circRNA inventories of mouse embryonic stem cells, neuronal progenitor cells and differentiated neurons and identify hundreds of highly expressed circRNAs. By screening several candidate circRNAs for a potential function in neuronal differentiation, we find that represses expression of key neuronal markers, suggesting that this molecule negatively regulates neuronal differentiation.
View Article and Find Full Text PDFThe ribonucleolytic exosome complex is central for nuclear RNA degradation, primarily targeting non-coding RNAs. Still, the nuclear exosome could have protein-coding (pc) gene-specific regulatory activities. By depleting an exosome core component, or components of exosome adaptor complexes, we identify ∼2900 transcription start sites (TSSs) from within pc genes that produce exosome-sensitive transcripts.
View Article and Find Full Text PDFThe RNA exosome is involved in RNA processing and quality control. In humans, it consists of an enzymatically inactive nine-subunit core, with ribonucleolytic activity contributed by one or two additional components. Moreover, several protein cofactors interact with the exosome to enable and specify its recruitment to a wide range of substrates.
View Article and Find Full Text PDFPluripotent embryonic stem cells (ESCs) constitute an essential cellular niche sustained by epigenomic and transcriptional regulation. Any role of post-transcriptional processes remains less explored. Here, we identify a link between nuclear RNA levels, regulated by the poly(A) RNA exosome targeting (PAXT) connection, and transcriptional control by the polycomb repressive complex 2 (PRC2).
View Article and Find Full Text PDFPhilos Trans R Soc Lond B Biol Sci
November 2018
A polyA (pA) tail is an essential modification added to the 3' ends of a wide range of RNAs at different stages of their metabolism. Here, we describe the main sources of polyadenylation and outline their underlying biochemical interactions within the nuclei of budding yeast , human cells and, when relevant, the fission yeast Polyadenylation mediated by the Trf4/5 enzymes, and their human homologues PAPD5/7, typically leads to the 3'-end trimming or complete decay of non-coding RNAs. By contrast, the primary function of canonical pA polymerases (PAPs) is to produce stable and nuclear export-competent mRNAs.
View Article and Find Full Text PDFGene expression programs change during cellular transitions. It is well established that a network of transcription factors and chromatin modifiers regulate RNA levels during embryonic stem cell (ESC) differentiation, but the full impact of post-transcriptional processes remains elusive. While cytoplasmic RNA turnover mechanisms have been implicated in differentiation, the contribution of nuclear RNA decay has not been investigated.
View Article and Find Full Text PDFMammalian gene promoters and enhancers share many properties. They are composed of a unified promoter architecture of divergent transcripton initiation and gene promoters may exhibit enhancer function. However, it is currently unclear how expression strength of a regulatory element relates to its enhancer strength and if the unifying architecture is conserved across Metazoa.
View Article and Find Full Text PDFMost mammalian protein-coding gene promoters are divergent, yielding promoter upstream transcripts (PROMPTs) in the reverse direction from their conventionally produced mRNAs. PROMPTs are rapidly degraded by the RNA exosome rendering a general function of these molecules elusive. Yet, levels of certain PROMPTs are altered in stress conditions, like the DNA damage response (DDR), suggesting a possible regulatory role for at least a subset of these molecules.
View Article and Find Full Text PDFH3K4me3 is a histone modification that accumulates at the transcription-start site (TSS) of active genes and is known to be important for transcription activation. The way in which H3K4me3 is regulated at TSS and the actual molecular basis of its contribution to transcription remain largely unanswered. To address these questions, we have analyzed the contribution of dKDM5/LID, the main H3K4me3 demethylase in Drosophila, to the regulation of the pattern of H3K4me3.
View Article and Find Full Text PDFIn this article, we characterize histone demethylase activity of the entire family of JmjC+N proteins of Drosophila melanogaster. Our results show that Lid (little imaginal discs), which is structurally homologous to JARID1, demethylates H3K4me3. However, contrary to what would be inferred from its demethylase activity, lid contributes to the establishment of transcriptionally competent chromatin states as: (i) is required for histone H3 acetylation; (ii) contributes to expression of the homoeotic gene Ultrabithorax (Ubx); and (iii) antagonizes heterochromatin-mediated gene silencing (PEV).
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