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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 119,012 papers from 513,246 authors.

Most tweeted biology preprints, last 24 hours

in category molecular biology

*There are gaps in historical Twitter data, most notably in spring 2020. This may result in some preprints appearing with less tweets than they should.

11 results found. For more information, click each entry to expand.

1: Pervasive non-CpG methylation at zebrafish mosaic satellite repeats
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Posted 14 May 2020

Pervasive non-CpG methylation at zebrafish mosaic satellite repeats
4 tweets bioRxiv molecular biology

Samuel E Ross, Allegra Angeloni, Alex de Mendoza, Ozren Bogdanovic

In vertebrates, DNA methylation predominantly occurs at CG dinucleotides even though widespread non-CG methylation (mCH) has been reported in mammalian embryonic and neural cells. Unlike in mammals, where mCH is found enriched at CAC/G trinucleotides and is tissue-restricted, we find that zebrafish embryos as well as adult somatic and germline tissues display robust methylation enrichment at TGCT positions associated with mosaic satellite repeats. These repeats reside in H3K9me3-marked heterochromatin and display mCH reprogramming coincident with zygotic genome activation. Altogether, this work provides insight into a novel form of vertebrate mCH and highlights the substrate diversity of vertebrate DNA methyltransferases. ### Competing Interest Statement The authors have declared no competing interest.

2: The rocaglate CR-31-B (-) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo
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Posted 24 Nov 2020

The rocaglate CR-31-B (-) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo
4 tweets bioRxiv molecular biology

Arnold Gruenweller, Christin Mueller, Wiebke Obermann, Nadja Karl, Hans G. Wendel, Gaspar Taroncher-Oldenburg, Stephan Pleschka, Roland K. Hartmann, John Ziebuhr

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a betacoronavirus in the subgenus Sarbecovirus causes a respiratory disease with varying symptoms referred to as coronavirus disease 2019 (COVID-19) and is responsible for a pandemic that started in early 2020. With no vaccines or effective antiviral treatments available, and infection and fatality numbers continuing to increase globally, the quest for novel therapeutic solutions remains an urgent priority. Rocaglates, a class of plant-derived cyclopenta[b]benzofurans, exhibit broad-spectrum antiviral activity against positive- and negative-sense RNA viruses. This compound class inhibits eukaryotic initiation factor 4A (eIF4A)-dependent mRNA translation initiation, resulting in strongly reduced viral RNA translation. The synthetic rocaglate CR-31-B (-) has previously been shown to inhibit the replication of human coronaviruses, such as HCoV-229E and MERS-CoV, as well as Zika-, Lassa-, Crimean Congo hemorrhagic fever virus in primary cells. Here, we assessed the antiviral activity of CR-31-B (-) against SARS-CoV-2 using both in vitro and ex vivo cell culture models. In African green monkey Vero E6 cells, CR-31-B (-) inhibited SARS-CoV-2 replication with an EC50 of ~1.8 nM. In line with this, viral protein accumulation and replication/transcription complex formation were found to be strongly reduced by this compound. In an ex vivo infection system using human airway epithelial cells, CR-31-B (-) was found to cause a massive reduction of SARS-CoV-2 titers by about 4 logs to nearly non-detectable levels. The data reveal a potent anti-SARS-CoV-2 activity by CR-31-B (-), corroborating previous results obtained for other coronaviruses and supporting the idea that rocaglates may be used in first-line antiviral intervention strategies against novel and emerging RNA virus outbreaks.

3: TENT4A poly(A) polymerase regulates translesion DNA synthesis and is mutated in endometrial cancer
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Posted 03 Dec 2020

TENT4A poly(A) polymerase regulates translesion DNA synthesis and is mutated in endometrial cancer
4 tweets bioRxiv molecular biology

Umakanta Swain, Urmila Sehrawat, Avital Sarusi-Portuguez, Gilgi Friedlander, Ron Rotkopf, Charlotte Ebert, Tamar Paz-Elizur, Rivka Dikstein, Thomas Carell, Nicholas Geacintov, Zvi Livneh

TENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little is known. Here we focus on its multilayer regulation of translesion DNA synthesis (TLS), in which DNA lesions are bypassed by error-prone DNA polymerases. We show that TENT4A regulates mRNA stability and/or translation of DNA polymerase {eta} and RAD18 E3 ligase, which guides the polymerase to replication stalling sites, and monoubiquitinates PCNA, thereby enabling recruitment of error-prone DNA polymerases to damaged DNA sites. Remarkably, in addition to the effect on RAD18 mRNA stability via controlling its poly(A) tail, TENT4A indirectly regulates RAD18 via the tumor suppressor CYLD, and via the long non-coding antisense RNA PAXIP1-AS2, which had no known function. Knocking down the expression of TENT4A or CYLD, or overexpression of PAXIP1-AS2 led each to reduced amounts of the RAD18 protein and DNA polymerase {eta}, leading to reduced TLS, highlighting PAXIP1-AS2 as a new TLS regulator. Bioinformatics analysis revealed that TLS error-prone DNA polymerase genes and their TENT4A-related regulators are frequently mutated in endometrial cancer genomes, suggesting that TLS is dysregulated in this cancer.

4: CONTAIN: An open-source shipping container laboratory optimised for automated COVID-19 diagnostics
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Posted 20 May 2020

CONTAIN: An open-source shipping container laboratory optimised for automated COVID-19 diagnostics
2 tweets bioRxiv molecular biology

Kenneth T. Walker, Matthew Donora, Anthony Thomas, Alexander James Phillips, Krishma Ramgoolam, Kjara S Pilch, Phil Oberacker, Tomasz Piotr Jurkowski, Rares Marius Gosman, Aubin Fleiss, Alex Perkins, Neil MacKenzie, Mark Zuckerman, Davide Danovi, Helene Steiner, Thomas Meany

The COVID-19 pandemic has challenged diagnostic systems globally. Expanding testing capabilities to conduct population-wide screening for COVID-19 requires innovation in diagnostic services at both the molecular and industrial scale. No report to-date has considered the complexity of laboratory infrastructure in conjunction with the available molecular assays to offer a standardised solution to testing. Here we present CONTAIN. A modular biosafety level 2+ laboratory optimised for automated RT-qPCR COVID-19 testing based on a standard 40ft shipping container. Using open-source liquid-handling robots and RNA extraction reagents we demonstrate a reproducible workflow for RT-qPCR COVID-19 testing. With five OT2 liquid handlers, a single CONTAIN unit reaches a maximum daily testing capacity of 2400 tests/day. We validate this workflow for automated RT-qPCR testing, using both synthetic SARS-CoV-2 samples and patient samples from a local NHS hospital. Finally, we discuss the suitability of CONTAIN and its flexibility in a range of diagnostic testing scenarios including high-density urban environments and mobile response units. ### Competing Interest Statement The authors have declared no competing interest.

5: Zinc finger protein SALL4 functions through an AT-rich motif to regulate gene expression
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Posted 04 Jul 2020

Zinc finger protein SALL4 functions through an AT-rich motif to regulate gene expression
2 tweets bioRxiv molecular biology

Nikki R. Kong, Mahmoud A. Bassal, Hong Kee Tan, Jesse V. Kurland, Kol Jia Yong, John J. Young, Yang Yang, Fudong Li, Jonathan Lee, Yue Liu, Chan-Shuo Wu, Alicia Stein, Hongbo Luo, Leslie E. Silberstein, Martha L. Bulyk, Daniel G Tenen, Li Chai

The zinc finger transcription factor SALL4 is highly expressed in embryonic stem cells, down-regulated in most adult tissues, but reactivated in many aggressive cancers. This unique expression pattern makes SALL4 an attractive target for designing therapeutic strategies. However, whether SALL4 binds DNA directly to regulate gene expression is unclear and many of its targets in cancer cells remain elusive. Here, through an unbiased screen of protein binding microarray (PBM) and Cleavage Under Targets and Release Using Nuclease (CUT&RUN) experiments, we identified and validated the DNA binding domain of SALL4 and its consensus binding sequence. Combined with RNA-seq analyses after SALL4 knockdown, we discovered hundreds of new SALL4 target genes that it directly regulates in aggressive liver cancer cells, including genes encoding a family of Histone 3 Lysine 9-specific Demethylases (KDMs). Taken together, these results elucidated the mechanism of SALL4 DNA binding and revealed novel pathways and molecules to target in SALL4-dependent tumors. ### Competing Interest Statement The authors have declared no competing interest.

6: Method comparison studies of telomere length measurement using qPCR approaches: a critical appraisal of the literature
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Posted 04 Sep 2020

Method comparison studies of telomere length measurement using qPCR approaches: a critical appraisal of the literature
1 tweet bioRxiv molecular biology

Alyssa R. Lindrose, Lauren W.Y. McLester-Davis, Renee I. Tristano, Leila Kataria, Shahinaz M. Gadalla, Dan T. A. Eisenberg, Simon Verhulst, Stacy Drury

Use of telomere length (TL) as a biomarker for various environmental exposures and diseases has increased in recent years. Various methods have been developed to measure telomere length. PCR-based methods remain wide-spread for population-based studies due to the high-throughput capability. While several studies have evaluated TL measurement methods, the results have been variable.   We conducted a literature review of TL measurement cross-method comparison studies that included a PCR-based method published between January 1, 2002 and May 25, 2020. A total of 20 articles were found that matched the inclusion criteria. Papers were reviewed for quality of methodologic reporting of sample and DNA quality, PCR assay characteristics, and analytic approaches to determine final TL was low as assessed by two different recommended reporting guidelines. Additionally, few papers reported whether samples were blinded for analysis. Reported correlation between methods (as assessed by Pearson’s r) varied, as did reported coefficients of variation or intra-class correlation coefficient. The sample size for nearly all studies was less than 100, raising significant concerns about statistical power. Overall, this review found that the current literature on the relation between TL measurement methods is lacking in validity and scientific rigor. To assist future investigators, we present recommendations for reporting guidelines of PCR-based TL measurement methods and present data to demonstrate the impact of assay variability on statistical power. Future cross-laboratory studies with rigorous methodologic and statistical reporting, adequate sample size, and blinding are essential to determine the true relation and variability of various TL measurement methods and are a key directive to the newly initiated Telomere Research Network funded jointly by then NIA and NIEHS. ### Competing Interest Statement The authors have declared no competing interest.

7: CUT&RUN detects distinct DNA footprints of RNA polymerase II near the transcription start sites
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Posted 07 Jul 2020

CUT&RUN detects distinct DNA footprints of RNA polymerase II near the transcription start sites
1 tweet bioRxiv molecular biology

Michi Miura, Honglin Chen

CUT&RUN is a powerful tool to study protein-DNA interactions in vivo . DNA fragments cleaved by the targeted micrococcal nuclease identify the footprints of DNA-binding proteins on the chromatin. We performed CUT&RUN on human lung carcinoma cell line A549 maintained in a multi-well cell culture plate to profile RNA polymerase II. Long (>270 bp) DNA fragments released by CUT&RUN corresponded to the bimodal peak around the transcription start sites, as previously seen with chromatin immunoprecipitation. However, we found that short (<120 bp) fragments identify a well-defined peak localised at the transcription start sites. This distinct DNA footprint of short fragments, which constituted only about 5% of the total reads, suggests the transient positioning of RNA polymerase II before promoter-proximal pausing, which has not been detected in the physiological settings by standard chromatin immunoprecipitation. We showed that the positioning of the large-size-class DNA footprints around the short-fragment peak was associated with the directionality of transcription, demonstrating the biological significance of distinct CUT&RUN footprints of RNA polymerase II. ### Competing Interest Statement The authors have declared no competing interest. * CUT&RUN : Cleavage Under Targets and Release Using Nuclease pAG-MNase : Protein A/G-fused micrococcal nuclease ChIP : chromatin immunoprecipitation Pol II : RNA polymerase II TSS : transcription start site S5p Pol II : Serine 5-phosphorylated RNA polymerase II mNET-seq : mammalian native elongating transcript-sequencing

8: Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming
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Posted 31 Jul 2019

Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming
1 tweet bioRxiv molecular biology

Yuancheng Lu, Anitha Krishnan, Benedikt Brommer, Xiao Tian, Margarita Meer, Daniel L. Vera, Chen Wang, Qiurui Zeng, Doudou Yu, Michael S. Bonkowski, Jae-Hyun Yang, Emma M. Hoffmann, Songlin Zhou, Ekaterina Korobkina, Noah Davidsohn, Michael B. Schultz, Karolina Chwalek, Luis A. Rajman, George Church, Konrad Hochedlinger, Vadim N Gladyshev, Steve Horvath, Meredith S. Gregory-Ksander, Bruce R. Ksander, Zhigang He, David A. Sinclair

Ageing is a degenerative process leading to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise, which disrupts youthful gene expression patterns that are required for cells to function optimally and recover from damage. Changes to DNA methylation patterns over time form the basis of an 'ageing clock', but whether old individuals retain information to reset the clock and, if so, whether this would improve tissue function is not known. Of all the tissues in the body, the central nervous system (CNS) is one of the first to lose regenerative capacity. Using the eye as a model tissue, we show that expression of Oct4, Sox2, and Klf4 genes (OSK) in mice resets youthful gene expression patterns and the DNA methylation age of retinal ganglion cells, promotes axon regeneration after optic nerve crush injury, and restores vision in a mouse model of glaucoma and in normal old mice. This process, which we call recovery of information via epigenetic reprogramming or REVIVER, requires the DNA demethylases Tet1 and Tet2, indicating that DNA methylation patterns don't just indicate age, they participate in ageing. Thus, old tissues retain a faithful record of youthful epigenetic information that can be accessed for functional age reversal.

9: Global increase in circRNA levels in myotonic dystrophy
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Posted 07 Dec 2018

Global increase in circRNA levels in myotonic dystrophy
1 tweet bioRxiv molecular biology

Karol Czubak, Katarzyna Taylor, Agnieszka Piasecka, Krzysztof Sobczak, Katarzyna Kozlowska, Anna Philips, Saam Sedehizadeh, J. David Brook, Marzena Wojciechowska, Piotr Kozlowski

Splicing aberrations induced as a consequence of the sequestration of MBNL splicing factors on the DMPK transcript, which contains expanded CUG repeats, present a major pathomechanism of myotonic dystrophy type 1 (DM1). As MBNLs may also be important factors involved in the biogenesis of circular RNAs (circRNAs), we hypothesized that the level of circRNAs would be decreased in DM1. To test this hypothesis, we selected twenty well-validated circRNAs and analyzed their levels in several experimental systems (e.g., cell lines, DM muscle tissues, and a mouse model of DM1) using droplet digital PCR assays. We also explored the global level of circRNAs using two RNA-Seq datasets of DM1 muscle samples. Contrary to our original hypothesis, our results consistently showed a global increase in circRNA levels in DM1 and we identified numerous circRNAs that were increased in DM1. We also identified many genes (including muscle-specific genes) giving rise to numerous (>10) circRNAs. Thus, this study is the first to show an increase in global circRNA levels in DM1. We also provided preliminary results showing the association of circRNA level with muscle weakness and alternative splicing changes that are biomarkers of DM1 severity.

10: FACT is recruited to the +1 nucleosome of transcribed genes and spreads in a Chd1-dependent manner
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Posted 21 Aug 2020

FACT is recruited to the +1 nucleosome of transcribed genes and spreads in a Chd1-dependent manner
1 tweet bioRxiv molecular biology

Celia Jeronimo, Andrew Angel, Christian Poitras, Pierre Collin, Jane Mellor, François Robert

The histone chaperone FACT occupies transcribed regions where it plays prominent roles in maintaining chromatin integrity and preserving epigenetic information. How it is targeted to transcribed regions, however, remains unclear. Proposed models for how FACT finds its way to transcriptionally active chromatin include docking on the RNA polymerase II (RNAPII) C-terminal domain (CTD), recruitment by elongation factors, recognition of modified histone tails and binding partially disassembled nucleosomes. Here, we systematically tested these and other scenarios in Saccharomyces cerevisiae and found that FACT binds transcribed chromatin, not RNAPII. Through a combination of experimental and mathematical modeling evidence, we propose that FACT recognizes the +1 nucleosome, as it is partially unwrapped by the engaging RNAPII, and spreads to downstream nucleosomes aided by the chromatin remodeler Chd1. Our work clarifies how FACT interacts with genes, suggests a processive mechanism for FACT function, and provides a framework to further dissect the molecular mechanisms of transcription-coupled histone chaperoning. ### Competing Interest Statement The authors have declared no competing interest.

11: A unique view of SARS-CoV-2 through the lens of ORF8 protein
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Posted 26 Aug 2020

A unique view of SARS-CoV-2 through the lens of ORF8 protein
1 tweet bioRxiv molecular biology

Sk. Sarif Hassan, Shinjini Ghosh, Diksha Attrish, Pabirtra Pal Choudhury, Murat Seyran, Damiano Pizzol, Parise Adadi, Tarek Muhammed Abd El Aziz, Antonio Soares, Ramesh Kandimalla, Kenneth Lundstrom, Murtaza Tambuwala, Alaa AA Aljabali, Amos Lal, Gajendra Kumar Azad, Vladimir N Uversky, Samendra P Sherchan, Wagner Baetas-da-Cruz, Bruce Uhal, Nima Rezaei, Adam Brufsky

Immune evasion is one of the unique characteristics of COVID-19 attributed to the ORF8 protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This protein is involved in modulating the host adaptive immunity through down-regulating MHC (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the interferon mediated antiviral response of the host. To understand the immune perspective of the host with respect to the ORF8 protein, a comprehensive study of the ORF8 protein as well as mutations possessed by it, is performed. Chemical and structural properties of ORF8 proteins from different hosts, that is human, bat and pangolin, suggests that the ORF8 of SARS-CoV-2 and Bat RaTG13-CoV are very much closer related than that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 (SARS-CoV-2) are grouped into four classes based on their predicted effects. Based on geo- locations and timescale of collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were endorsed upon sequence similarity and amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of rapid evolving SARS-CoV-2 through the ORF8. ### Competing Interest Statement The authors have declared no competing interest.


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