scholarly journals Alteration of epigenetic landscape by lamin A mutations: Hallmark of Dilated Cardiomyopathy

2020 ◽  
Author(s):  
Avinanda Banerjee ◽  
Kaushik Sengupta

AbstractMutations in lamin A have been reported to be associated with over 16 human diseases including dilated cardiomyopathy (DCM). We have focused on three such DCM causing mutants of lamin A which have to address the contribution of lamins in the pathogenesis of DCM at molecular level. We have elucidated the effect of these mutants for the first time on the epigenetic landscape of a myogenic fibroblast cell line C2C12. C2C12 cells expressing these mutant proteins exhibited alterations in some histone modification marks like H3K4me3, H3K9me3, H3K27me3, H3K36me3 and RNA Polymerase II activity compared to its wild type variants. This report paves the way for further studies involving epigenetic regulation in laminopathies which would be an important step in explaining the molecular mechanism and pathophysiology of the diseases like dilated cardiomyopathy.High Lightslamin A K97E mutation predominantly alters H3K9me3 histone modifications landscapelamin A K97E aggregates within nucleus also sequester the HP1γlamin A K97E mutation affects RNA polymerase II distribution pattern

Diversity ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 666
Author(s):  
Phongeun Sysouphanthong ◽  
Naritsada Thongklang ◽  
Jian-Kui Liu ◽  
Else C. Vellinga

In our ongoing research on lepiotaceous taxa (Agaricaceae s.l.) in Laos and northern Thailand, we focus here on Chlorophyllum, Clarkeinda, Macrolepiota, Pseudolepiota, and Xanthagaricus. Collections were obtained from various habitats, including agricultural habitats, grasslands, and rainforests. A total of 12 taxa were examined and investigated. Of these 12, two are new for science; viz. Xanthagaricus purpureosquamulosus with brownish-grey to violet-brown squamules on a pale-violet to violet background; it shares the pileus color with X. caeruleus and X. ianthinus, but differs in other characters; and Macrolepiota excelsa, rather similar to M. procera but related toM. detersa. Two species, Pseudolepiota zangmui and Xanthagaricus necopinatus are recorded for the first time in Thailand. Four species of Chlorophyllum and a total of four species of Macrolepiota were found, viz., C. demangei and C. hortense with white basidiospores, C. molybdites and C. globosum with green basidiospores, M. detersa, M. dolichaula, the new M. excelsa, and M. velosa. Another rather common striking species is Clarkeinda trachodes, with yellow-green basidiospores. Each species is described in detail, with color photographs and line drawings. Phylogenetic analyses based on internal transcribed spacer (nrITS) region, the large subunit nuclear ribosomal (nrLSU) DNA and RNA polymerase II second largest subunit (rpb2) genes provide evidence for the placement of the species covered.


2020 ◽  
Author(s):  
Toni Beltran ◽  
Elena Pahita ◽  
Subhanita Ghosh ◽  
Boris Lenhard ◽  
Peter Sarkies

AbstractPiwi-interacting RNAs (piRNAs) play key roles in germline development and genome defence in metazoans. In C. elegans, piRNAs are transcribed from >15000 discrete genomic loci by RNA polymerase II, resulting in 28 nt short-capped piRNA precursors. Here we investigate transcription termination at piRNA loci. We show that the Integrator complex, which terminates snRNA transcription, is recruited to piRNA loci. We show that the catalytic activity of Integrator cleaves nascent capped piRNA precursors associated with promoter-proximal Pol II, resulting in termination of transcription. Loss of Integrator activity, however, does not result in transcriptional readthrough at the majority of piRNA loci. Our results draw new parallels between snRNA and piRNA biogenesis in nematodes, and provide evidence of a role for the Integrator complex as a terminator of promoter-proximal RNA polymerase II.Highlights- Integrator localises to sites of piRNA biogenesis in nematodes- Integrator cleaves nascent RNAs associated with promoter-proximal Pol II at piRNA loci to release short capped piRNA precursors from chromatin- Repression of Pol II elongation at the majority of piRNA loci is independent of Integrator


1990 ◽  
Vol 10 (11) ◽  
pp. 6059-6063 ◽  
Author(s):  
M F LeMaire ◽  
C S Thummel

The E74 gene is one of a small set of early genes induced by the steroid hormone ecdysone at the onset of metamorphosis in the fruit fly, Drosophila melanogaster. This complex gene directs the synthesis of a 60-kilobase (kb) primary transcript that is spliced to form the 6-kb E74A mRNA. In a previous study, we found that ecdysone directly activates the E74A promoter and determined that RNA polymerase II transcribes this gene at a rate of approximately 1.1 kb/min. This elongation rate accounts for most of the 1-hour delay seen between the addition of ecdysone and the appearance of cytoplasmic E74A mRNA (C. S. Thummel, K. C. Burtis, and D. S. Hogness, Cell 61:101-111, 1990). We show here that nascent E74A transcripts are spliced, and we propose a model for the order of that splicing. This study provides, for the first time, direct biochemical evidence for splicing of a low-abundance cellular RNA before transcription termination and polyadenylation.


Phytotaxa ◽  
2014 ◽  
Vol 189 (1) ◽  
pp. 52 ◽  
Author(s):  
Ekaphan Kraichak ◽  
Sittiporn Parnmen ◽  
Robert Lücking ◽  
EIMY RIVAS PLATA ◽  
André Aptroot ◽  
...  

We present an updated 3-locus molecular phylogeny of tribe Ocellularieae, the second largest tribe within subfamily Graphidoideae in the Graphidaceae. Adding 165 newly generated sequences from the mitochondrial small subunit rDNA (mtSSU), the nuclear large subunit rDNA (nuLSU), and the second largest subunit of the DNA-directed RNA polymerase II (RPB2), we currently distinguish 218 species among the sequenced material, including the outgroup. This corresponds to almost half the species at this point recognized within this tribe. The newly generated sequences include 23 newly described species and one newly described genus published elsewhere in this volume. For the first time, Sarcographina cyclospora Müll. Arg., in spite of its distinctly lirellate ascomata, is shown to belong in tribe Ocellularieae, as strongly supported sister to Ocellularia inturgescens (Müll. Arg.) Mangold. The following six new combinations are proposed: Melanotrema lynceodes (Nyl.) Rivas Plata, Lücking & Lumbsch, Ocellularia curranii (Vain.) Kraichak, Lücking & Lumbsch, O. khasiana (Patw. & Nagarkar) Kraichak, Lücking & Lumbsch, O. cinerea (Müll. Arg.) Kraichak, Lücking & Lumbsch, O. erodens (R. C. Harris) Kraichak, Lücking & Lumbsch, and O. laeviuscula (Nyl) Kraichak, Lücking & Lumbsch. Further, the new name Ocellularia hernandeziana Kraichak, Lücking & Lumbsch is introduced for Myriotrema ecorticatum. The nomenclatural status of the name Ocellularia microstoma is clarified.


2020 ◽  
Author(s):  
Yaqing Zhang ◽  
David Kuster ◽  
Tobias Schmidt ◽  
Daniel Kirrmaier ◽  
Gabriele Nübel ◽  
...  

SummaryThe ubiquitous redox coenzyme nicotinamide adenine dinucleotide (NAD) acts as a non-canonical cap structure on prokaryotic and eukaryotic ribonucleic acids. Here we find that in budding yeast, NAD-RNAs are abundant (>1400 species), short (<170 nt), and mostly correspond to mRNA 5’-ends. The modification percentage is low (<5%). NAD is incorporated during the initiation step by RNA polymerase II, which uses distinct promoters with a YAAG core motif for this purpose. Most NAD-RNAs are 3’-truncated. At least three decapping enzymes, Rai1, Dxo1, and Npy1, guard against NAD-RNA at different cellular locations, targeting overlapping transcript populations. NAD-mRNAs do not support translation in vitro. Our work indicates that in budding yeast, most of the NAD incorporation into RNA seems to be accidental and undesirable to the cell, which has evolved a diverse surveillance machinery to prematurely terminate, decap and reject NAD-RNAs.In BriefIn budding yeast, most of the NAD incorporation into RNA seems to be accidental and undesirable to the cell, which has evolved a diverse surveillance machinery to prematurely terminate, decap and reject NAD-RNAs.Graphical AbstractHighlightsYeast cells have thousands of short NAD-RNAs related to the 5’-ends of mRNAsRNA polymerase II prefers a YAAG promoter motif for NAD incorporation into RNANAD-RNA is strongly guarded against by Rai1, Dxo1, and Npy1 decapping enzymes at different subcellular sitesIn vitro, NAD-mRNAs are rejected from translation


2017 ◽  
Author(s):  
Massimiliano Bonomi ◽  
Samuel Hanot ◽  
Charles H. Greenberg ◽  
Andrej Sali ◽  
Michael Nilges ◽  
...  

SummaryCryo-electron microscopy (cryo-EM) has become a mainstream technique for determining the structures of complex biological systems. However, accurate integrative structural modeling has been hampered by the challenges in objectively weighing cryo-EM data against other sources of information due to the presence of random and systematic errors, as well as correlations, in the data. To address these challenges, we introduce a Bayesian scoring function that efficiently and accurately ranks alternative structural models of a macromolecular system based on their consistency with a cryo-EM density map and other experimental and prior information. The accuracy of this approach is benchmarked using complexes of known structure and illustrated in three applications: the structural determination of the GroEL/GroES, RNA polymerase II, and exosome complexes. The approach is implemented in the open-source Integrative Modeling Platform (http://integrativemodeling.org), thus enabling integrative structure determination by combining cryo-EM data with other sources of information.HighlightsWe present a modeling approach to integrate cryo-EM data with other sources of informationWe benchmark our approach using synthetic data on 21 complexes of known structureWe apply our approach to the GroEL/GroES, RNA polymerase II, and exosome complexes


2020 ◽  
Author(s):  
Nicolle A. Rosa-Mercado ◽  
Joshua T. Zimmer ◽  
Maria Apostolidi ◽  
Jesse Rinehart ◽  
Matthew D. Simon ◽  
...  

SummaryStress-induced readthrough transcription results in the synthesis of thousands of downstream-of-gene (DoG) containing transcripts. The mechanisms underlying DoG formation during cellular stress remain unknown. Nascent transcription profiles during DoG induction in human cell lines using TT-TimeLapse-seq revealed that hyperosmotic stress induces widespread transcriptional repression. Yet, DoGs are produced regardless of the transcriptional level of their upstream genes. ChIP-seq confirmed that the stress-induced redistribution of RNA Polymerase (Pol) II correlates with the transcriptional output of genes. Stress-induced alterations in the Pol II interactome are observed by mass spectrometry. While subunits of the cleavage and polyadenylation machinery remained Pol II-associated, Integrator complex subunits dissociated from Pol II under stress conditions. Depleting the catalytic subunit of the Integrator complex, Int11, using siRNAs induces hundreds of readthrough transcripts, whose parental genes partially overlap those of stress-induced DoGs. Our results provide insights into the mechanisms underlying DoG production and how Integrator activity influences DoG transcription.In briefRosa-Mercado et al. report that hyperosmotic stress causes widespread transcriptional repression in human cells, yet DoGs arise regardless of the transcriptional response of their upstream genes. They find that the interaction between Pol II and Integrator is disrupted by hypertonicity and that knocking down the Integrator nuclease leads to DoG production.HighlightsHyperosmotic stress triggers transcriptional repression of many genes.DoG RNAs arise independent of the transcriptional level of their upstream gene.The interaction between Pol II and Integrator subunits decreases after salt stress.Depletion of the Int11 nuclease subunit induces the production of hundreds of DoGs.


1990 ◽  
Vol 10 (11) ◽  
pp. 6059-6063
Author(s):  
M F LeMaire ◽  
C S Thummel

The E74 gene is one of a small set of early genes induced by the steroid hormone ecdysone at the onset of metamorphosis in the fruit fly, Drosophila melanogaster. This complex gene directs the synthesis of a 60-kilobase (kb) primary transcript that is spliced to form the 6-kb E74A mRNA. In a previous study, we found that ecdysone directly activates the E74A promoter and determined that RNA polymerase II transcribes this gene at a rate of approximately 1.1 kb/min. This elongation rate accounts for most of the 1-hour delay seen between the addition of ecdysone and the appearance of cytoplasmic E74A mRNA (C. S. Thummel, K. C. Burtis, and D. S. Hogness, Cell 61:101-111, 1990). We show here that nascent E74A transcripts are spliced, and we propose a model for the order of that splicing. This study provides, for the first time, direct biochemical evidence for splicing of a low-abundance cellular RNA before transcription termination and polyadenylation.


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