Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging

Disruption of the circadian clock, which directs rhythmic expression of numerous output genes, accelerates aging. To enquire how the circadian system protects aging organisms, here we compare circadian transcriptomes in heads of young and old Drosophila melanogaster. The core clock and most output genes remained robustly rhythmic in old flies, while others lost rhythmicity with age, resulting in constitutive over- or under-expression. Unexpectedly, we identify a subset of genes that adopted increased or de novo rhythmicity during aging, enriched for stress-response functions. These genes, termed late-life cyclers, were also rhythmically induced in young flies by constant exposure to exogenous oxidative stress, and this upregulation is CLOCK-dependent. We also identify age-onset rhythmicity in several putative primary piRNA transcripts overlapping antisense transposons. Our results suggest that, as organisms age, the circadian system shifts greater regulatory priority to the mitigation of accumulating cellular stress

A deep recurrent neural network discovers complex biological rules to decipher RNA protein-coding potential

The current deluge of newly identified RNA transcripts presents a singular opportunity for improved assessment of coding potential, a cornerstone of genome annotation, and for machine-driven discovery of biological knowledge. While traditional, feature-based methods for RNA classification are limited by current scientific knowledge, deep learning methods can independently discover complex biological rules in the data de novo. We trained a gated recurrent neural network (RNN) on human messenger RNA (mRNA) and long noncoding RNA (lncRNA) sequences. Our model, mRNA RNN (mRNN), surpasses state-of-the-art methods at predicting protein-coding potential despite being trained with less data and with no prior concept of what features define mRNAs. To understand what mRNN learned, we probed the network and uncovered several context-sensitive codons highly predictive of coding potential. Our results suggest that gated RNNs can learn complex and long-range patterns in full-length human transcripts, making them ideal for performing a wide range of difficult classification tasks and, most importantly, for harvesting new biological insights from the rising flood of sequencing data

PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells

Polycomb Repressive Complex 2 (PRC2) function and DNA methylation (DNAme) are typically correlated with gene repression. Here, we show that PRC2 is required to maintain expression of maternal microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) from the Gtl2-Rian-Mirg locus, which is essential for full pluripotency of iPSCs. In the absence of PRC2, the entire locus becomes transcriptionally repressed due to gain of DNAme at the intergenic differentially methylated regions (IG-DMRs). Furthermore, we demonstrate that the IG-DMR serves as an enhancer of the maternal Gtl2-Rian-Mirg locus. Further analysis reveals that PRC2 interacts physically with Dnmt3 methyltransferases and reduces recruitment to and subsequent DNAme at the IG-DMR, thereby allowing for proper expression of the maternal Gtl2-Rian-Mirg locus. Our observations are consistent with a mechanism through which PRC2 counteracts the action of Dnmt3 methyltransferases at an imprinted locus required for full pluripotency.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Elsevier. The published article can be found at: http://www.cell.com/cell-reports/hom

Diversity in Notch Ligand-Receptor Signaling Interactions

The ability to understand and predict signaling between different cell types is a major challenge in biology. The Notch pathway enables direct signaling through membrane-bound ligands and receptors, and is used in diverse contexts. While its canonical molecular signaling mechanism is well characterized, its many-to-many interacting pathway components, the complexity of their expression patterns, and the presence of same-cell (cis) as well as inter-cellular (trans) receptor-ligand interactions, have made it difficult to predict how a given cell will signal to others. Here, we use a cell-based approach, with Chinese hamster ovary (CHO-K1) cells and C2C12 mouse myoblasts, to systematically characterize trans-activation, cis-inhibition, and cis-activation efficiencies for the essential receptors (Notch1 and Notch2) and activating ligands (Dll1, Dll4, Jag1, and Jag2), in the presence of Lunatic Fringe (Lfng) or the enzymatically dead Lfng D289E mutant. All ligands trans-activate Notch1 and Notch2, except for Jag1, which competitively inhibits Notch1 signaling, and whose Notch1 binding strength is potentiated by Lfng. For Notch1, cis-activation is generally weaker than trans-activation, but for Notch2, cis-activation by Delta ligands is much stronger than trans-activation, and Notch2 cis-activation by Jag1 is similar in strength to trans-activation. Cis-inhibition is associated with weak cis-activation, as Dll1 and Dll4 do not cis-inhibit Notch2. Lfng expression potentiates trans-activation of both Notch1 and Notch2 by the Delta ligands and weakens trans-activation of both receptors by the Jagged ligands. The map of receptor-ligand-Fringe interaction outcomes revealed here should help guide rational perturbation and control of the Notch pathway

OPA Libraries open access panel.pdf

On March 31, 2016 the Oregon State University Postdoctoral Association and the Oregon State University Libraries hosted an open access panel moderated by Pedro Molina-Sanchez. Speakers included Michaela Willi Hooper, Scholarly Communication Librarian at OSU Libraries; Rachael Kuintzle, PhD student in the OSU College of Science; Marit Bovbjerg, Faculty in the OSU College of Public Health and Human Sciences; and Austin Fox, PhD student in the OSU College of Engineering. The presentation here consists of the publicity poster Pedro created and slides from Rachael, Austin, and Michaela. Marit did not use slides. The publicity poster contains the following description: "Publishing Open Access, which allows everyone free access to published manuscripts, has a significant impact on citation numbers and an overall positive effect on the dissemination of scholarly articles. Moreover, an Open Access model of publishing prevents us from paying twice for academic research! Come and join us at this panel discussion to learn about Open Access, one of the hottest topics in academic publishing, and contribute to the discussion on how we conduct and communicate our research.

What Is Open Access? Advance Your Career by Unlocking Your Work

On March 31, 2016 the Oregon State University Postdoctoral Association and the Oregon State University Libraries hosted an open access panel moderated by Pedro Molina-Sanchez. Speakers included Michaela Willi Hooper, Scholarly Communication Librarian at OSU Libraries; Rachael Kuintzle, PhD student in the OSU College of Science; Marit Bovbjerg, Faculty in the OSU College of Public Health and Human Sciences; and Austin Fox, PhD student in the OSU College of Engineering. The presentation here consists of the publicity poster Pedro created and slides from Rachael, Austin, and Michaela. Marit did not use slides. The publicity poster contains the following description: "Publishing Open Access, which allows everyone free access to published manuscripts, has a significant impact on citation numbers and an overall positive effect on the dissemination of scholarly articles. Moreover, an Open Access model of publishing prevents us from paying twice for academic research! Come and join us at this panel discussion to learn about Open Access, one of the hottest topics in academic publishing, and contribute to the discussion on how we conduct and communicate our research."Keywords: open access, scholarly communication, social justic

HendrixDavidEECSPRC2RequiredMaintainSupplementalInformationFiguresS1–S7andTablesS1–S7.pdf

Polycomb Repressive Complex 2 (PRC2) function and DNA methylation (DNAme) are typically correlated with gene repression. Here, we show that PRC2 is required to maintain expression of maternal microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) from the Gtl2-Rian-Mirg locus, which is essential for full pluripotency of iPSCs. In the absence of PRC2, the entire locus becomes transcriptionally repressed due to gain of DNAme at the intergenic differentially methylated regions (IG-DMRs). Furthermore, we demonstrate that the IG-DMR serves as an enhancer of the maternal Gtl2-Rian-Mirg locus. Further analysis reveals that PRC2 interacts physically with Dnmt3 methyltransferases and reduces recruitment to and subsequent DNAme at the IG-DMR, thereby allowing for proper expression of the maternal Gtl2-Rian-Mirg locus. Our observations are consistent with a mechanism through which PRC2 counteracts the action of Dnmt3 methyltransferases at an imprinted locus required for full pluripotency

HendrixDavidEECSPRC2RequiredMaintain.pdf

Polycomb Repressive Complex 2 (PRC2) function and DNA methylation (DNAme) are typically correlated with gene repression. Here, we show that PRC2 is required to maintain expression of maternal microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) from the Gtl2-Rian-Mirg locus, which is essential for full pluripotency of iPSCs. In the absence of PRC2, the entire locus becomes transcriptionally repressed due to gain of DNAme at the intergenic differentially methylated regions (IG-DMRs). Furthermore, we demonstrate that the IG-DMR serves as an enhancer of the maternal Gtl2-Rian-Mirg locus. Further analysis reveals that PRC2 interacts physically with Dnmt3 methyltransferases and reduces recruitment to and subsequent DNAme at the IG-DMR, thereby allowing for proper expression of the maternal Gtl2-Rian-Mirg locus. Our observations are consistent with a mechanism through which PRC2 counteracts the action of Dnmt3 methyltransferases at an imprinted locus required for full pluripotency

MicroRNA and gene expression changes in unruptured human cerebral aneurysms

OBJECTIVE The molecular mechanisms behind cerebral aneurysm formation and rupture remain poorly understood. In the past decade, microRNAs (miRNAs) have been shown to be key regulators in a host of biological processes. They are noncoding RNA molecules, approximately 21 nucleotides long, that posttranscriptionally inhibit mRNAs by attenuating protein translation and promoting mRNA degradation. The miRNA and mRNA interactions and expression levels in cerebral aneurysm tissue from human subjects were profiled. METHODS A prospective case-control study was performed on human subjects to characterize the differential expression of mRNA and miRNA in unruptured cerebral aneurysms in comparison with control tissue (healthy superficial temporal arteries [STA]). Ion Torrent was used for deep RNA sequencing. Affymetrix miRNA microarrays were used to analyze miRNA expression, whereas NanoString nCounter technology was used for validation of the identified targets. RESULTS Overall, 7 unruptured cerebral aneurysm and 10 STA specimens were collected. Several differentially expressed genes were identified in aneurysm tissue, with MMP-13 (fold change 7.21) and various collagen genes (COL1A1, COL5A1, COL5A2) being among the most upregulated. In addition, multiple miRNAs were significantly differentially expressed, with miR-21 (fold change 16.97) being the most upregulated, and miR-143–5p (fold change −11.14) being the most downregulated. From these, miR-21, miR-143, and miR-145 had several significantly anticorrelated target genes in the cohort that are associated with smooth muscle cell function, extracellular matrix remodeling, inflammation signaling, and lipid accumulation. All these processes are crucial to the pathophysiology of cerebral aneurysms. CONCLUSIONS This analysis identified differentially expressed genes and miRNAs in unruptured human cerebral aneurysms, suggesting the possibility of a role for miRNAs in aneurysm formation. Further investigation for their importance as therapeutic targets is needed

PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells

Polycomb Repressive Complex 2 (PRC2) function and DNA methylation (DNAme) are typically correlated with gene repression. Here, we show that PRC2 is required to maintain expression of maternal microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) from the Gtl2-Rian-Mirg locus, which is essential for full pluripotency of iPSCs. In the absence of PRC2, the entire locus becomes transcriptionally repressed due to gain of DNAme at the intergenic differentially methylated regions (IG-DMRs). Furthermore, we demonstrate that the IG-DMR serves as an enhancer of the maternal Gtl2-Rian-Mirg locus. Further analysis reveals that PRC2 interacts physically with Dnmt3 methyltransferases and reduces recruitment to and subsequent DNAme at the IG-DMR, thereby allowing for proper expression of the maternal Gtl2-Rian-Mirg locus. Our observations are consistent with a mechanism through which PRC2 counteracts the action of Dnmt3 methyltransferases at an imprinted locus required for full pluripotency