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The piRNA-pathway factor FKBP6 is essential for spermatogenesis butdispensable for control of meiotic LINE-1 expression in humans. Wyrwoll M.J. et al. Infertility affects around 7\% of the male population and can be due to severe spermatogenic failure (SPGF), resulting in no or very few sperm in the ejaculate. We initially identified a homozygous frameshift variant in FKBP6 in a man with extreme oligozoospermia. Subsequently, we screened a total of 2,699 men with ... |
The seminal plasma microbiome of men with testicular germ cell tumours described by small RNA sequencing Nina Mørup, Ailsa Maria Main, Niels Jørgensen, Gedske Daugaard, Anders Juul, Kristian Almstrup Background: It has been estimated that microorganisms are involved in the pathogenesis of approximately 20% of all cancers. Testicular germ cell tumours (TGCTs) are the most common type of malignancy in young men and arise from the precursor cell, Germ Cell Neoplasia in Situ (GCNIS). The microbiome of seminal p... |
Neutral sphingomyelinase 2 inhibition attenuates extracellular vesiclerelease and improves neurobehavioral deficits in murine HIV. Zhu X. et al. People living with HIV (PLH) have significantly higher rates of cognitive impairment (CI) and major depressive disorder (MDD) versus the general population. The enzyme neutral sphingomyelinase 2 (nSMase2) is involved in the biogenesis of ceramide and extracellular vesicles (EVs), both of which are dysregulated in PL... |
A novel, essential trans-splicing protein connects the nematode SL1snRNP to the CBC-ARS2 complex. Fasimoye Rotimi Yemi et al. Spliced leader trans-splicing is essential for gene expression in many eukaryotes. To elucidate the molecular mechanism of this process, we characterise the molecules associated with the Caenorhabditis elegans major spliced leader snRNP (SL1 snRNP), which donates the spliced leader that replaces the 5' untranslated ... |
Interspecies effectors of a transgenerational memory of bacterial infection in Caenorhabditis elegans . Legüe Marcela et al. The inheritance of memory is an adaptive trait. Microbes challenge the immunity of organisms and trigger behavioral adaptations that can be inherited, but how bacteria produce inheritance of a trait is unknown. We use and its bacteria to study the transgenerational RNA dynamics of interspecies crosstalk leading to a... |
Diverse Monogenic Subforms of Human Spermatogenic Failure Nagirnaja L. et al. Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable with current medicine. Due to the biological complexity of sperm production, defining the genetic basis of NOA has proven challenging, and to date, the most advanced classification of NOA subforms is based on simple... |
Ultrasensitive Ribo-seq reveals translational landscapes duringmammalian oocyte-to-embryo transition and pre-implantation development. Xiong Zhuqing et al. In mammals, translational control plays critical roles during oocyte-to-embryo transition (OET) when transcription ceases. However, the underlying regulatory mechanisms remain challenging to study. Here, using low-input Ribo-seq (Ribo-lite), we investigated translational landscapes during OET using 30-150 mouse oocy... |
Translation is a key determinant controlling the fate of cytoplasmic longnon-coding RNAs Andjus Sara et al. Despite predicted to lack coding potential, cytoplasmic long non-coding (lnc)RNAs can associate with ribosomes, resulting in some cases into the production of functional peptides. However, the biological and mechanistic relevance of this pervasive lncRNAs translation remains poorly studied. In yeast, cytoplasmic Xrn... |
MGcount: a total RNA-seq quantification tool to address multi-mappingand multi-overlapping alignments ambiguity in non-coding transcripts Hita Andrea, Brocart Gilles, Fernandez Ana, Rehmsmeier Marc, Alemany Anna, Schvartzman Sol Background Total-RNA sequencing (total-RNA-seq) allows the simultaneous study of both the coding and the non-coding transcriptome. Yet, computational pipelines have traditionally focused on particular biotypes, making assumptions that are not fullfilled by total-RNA-seq datasets. Transcripts from distinct RNA biotyp... |
Single cell quantification of ribosome occupancy in early mouse development Tori Tonn et al. Technological limitations precluded transcriptome-wide analyses of translation at single cell resolution. To solve this challenge, we developed a novel microfluidic isotachophoresis approach, named RIBOsome profiling via IsoTachoPhoresis (Ribo-ITP), and characterized translation in single oocytes and embryos during ... |
Single cell quantification of ribosome occupancy in early mousedevelopment Tonn T. et al. Technological limitations precluded transcriptome-wide analyses of translation at single cell resolution. To solve this challenge, we developed a novel microfluidic isotachophoresis approach, named RIBOsome profiling via IsoTachoPhoresis (Ribo-ITP), and characterized translation in single oocytes and embryos during ... |
Functional microRNA targetome undergoes degeneration-induced shift in the retina Chu-Tan JA et al.
Background: MicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases including age-related macular degeneration (AMD), acting as post-transcriptional gene suppressors through their association with argonaute 2 (AGO2) - a key member of the RNA Induced Silencing Complex... |
Functional microRNA targetome undergoes degeneration-induced shift inthe retina. Chu-Tan Joshua A et al. BACKGROUND: MicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases including age-related macular degeneration (AMD), acting as post-transcriptional gene suppressors through their association with argonaute 2 (AGO2) - a key member of the RNA Induced Silencing Complex (RISC)... |
Single-cell microRNA sequencing method comparison and application tocell lines and circulating lung tumor cells Hücker S. et al. Molecular single cell analyses provide insights into physiological and pathological processes. Here, in a stepwise approach, we first evaluate 19 protocols for single cell small RNA sequencing on MCF7 cells spiked with 1 pg of 1,006 miRNAs. Second, we analyze MCF7 single cell equivalents of the eight best pro... |
Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors Mørup N. et al. Circulating miRNAs secreted by testicular germ cell tumors (TGCT) show great potential as novel non-invasive biomarkers for diagnosis of TGCT. Seminal plasma (SP) represents a biofluid closer to the primary site. Here, we investigate whether small RNAs in SP can be used to diagnose men with TGCTs or the precursor le... |
Vesicle-bound regulatory RNAs are associated with tissue aging F. Kern, T. Kuhn, N. Ludwig, M. Simon, L. Gröger, N. Fabis, A. Salhab, T. Fehlmann, O. Hahn, A. Engel, M. Koch, J. Koehler, K. Winek, H. Soreq, G. Fuhrmann, T. Wyss-Coray, E. Meese, M. W. Laschke and A. Keller Previous work on murine models and human demonstrated global as well as tissue-specific molecular aging trajectories in solid tissues and body fluids1–8. Extracellular vesicles like exosomes play a crucial role in communication and information exchange in between such systemic factors and solid tissues9,10. We... |
Small RNAs in Seminal Plasma as Novel Biomarkers for GermCell Tumors. Mørup Nina et al. Circulating miRNAs secreted by testicular germ cell tumors (TGCT) show great potential as novel non-invasive biomarkers for diagnosis of TGCT. Seminal plasma (SP) represents a biofluid closer to the primary site. Here, we investigate whether small RNAs in SP can be used to diagnose men with TGCTs or the precursor le... |
miRMaster 2.0: multi-species non-coding RNA sequencing analyses at scale Tobias Fehlmann, Fabian Kern, Omar Laham, Christina Backes, Jeffrey Solomon, Pascal Hirsch, Carsten Volz, Rolf Müller, Andreas Keller Analyzing all features of small non-coding RNA sequencing data can be demanding and challenging. To facilitate this process, we developed miRMaster. After the analysis of over 125 000 human samples and 1.5 trillion human small RNA reads over 4 years, we present miRMaster 2 with a wide range of updates and new featur... |
Bacterial small RNAs and host epigenetic effectors of atransgenerational memory of pathogens in C. elegans Legüe M. et al. The inheritance of memories is adaptive for survival. Microbes interact with all organisms challenging their immunity and triggering behavioral adaptations. Some of these behaviors induced by bacteria can be inherited although the mechanisms of action are largely unexplored. In this work, we use C. elegans and its b... |
Interspecies RNA Interactome of Pathogen and Host in aHeritable Defensive Strategy. Legüe Marcela et al. Communication with bacteria deeply impacts the life history traits of their hosts. Through specific molecules and metabolites, bacteria can promote short- and long-term phenotypic and behavioral changes in the nematode . The chronic exposure of to pathogens promotes the adaptive behavior in the host's progeny called... |
Distinct Extracellular RNA Profiles in Different PlasmaComponents. Jia Jing et al. Circulating extracellular RNAs (exRNAs) have great potential to serve as biomarkers for a wide range of diagnostic, therapeutic, and prognostic applications. So far, knowledge of the difference among different sources of exRNAs is limited. To address this issue, we performed a sequential physical and biochemical pre... |
Genes with 5′ terminal oligopyrimidine tracts preferentially escapeglobal suppression of translation by the SARS-CoV-2 NSP1 protein Shilpa, Rao and Ian, Hoskins and P., Daniela Garcia and Tori, Tonn andHakan, Ozadam and Elif, Sarinay Cenik and ProfileCan, Cenik Viruses rely on the host translation machinery to synthesize their own proteins. Consequently, they have evolved varied mechanisms to co-opt host translation for their survival. SARS-CoV-2 relies on a non-structural protein, NSP1, for shutting down host translation. Despite this, it is currently unknown how viral pr... |
Repeat RNAs associate with replication forks and post-replicative DNA. Gylling HM, Gonzalez-Aguilera C, Smith MA, Kaczorowski DC, Groth A, Lund AH Non-coding RNA has a proven ability to direct and regulate chromatin modifications by acting as scaffolds between DNA and histone-modifying complexes. However, it is unknown if ncRNA plays any role in DNA replication and epigenome maintenance, including histone eviction and re-instalment of histone-modifications aft... |
The sncRNA Zoo: a repository for circulating small noncoding RNAs in animals. Fehlmann T, Backes C, Pirritano M, Laufer T, Galata V, Kern F, Kahraman M, Gasparoni G, Ludwig N, Lenhof HP, Gregersen HA, Francke R, Meese E, Simon M, Keller A The repertoire of small noncoding RNAs (sncRNAs), particularly miRNAs, in animals is considered to be evolutionarily conserved. Studies on sncRNAs are often largely based on homology-based information, relying on genomic sequence similarity and excluding actual expression data. To obtain information on sncRNA expres... |
NGS analysis of total small non coding RNAs from low input RNA from dried blood sampling Marcello Pirritano, Tobias Fehlmann, Thomas Laufer, Nicole Ludwig, Gilles Gasparoni, Yongping Li, Eckart Meese, Andreas Keller, and Martin Simon Circulating miRNAs are favored for biomarker candidates as they can reflect tissue specific miRNA dysregulation in disease contexts. Moreover, they have additional advantages that they can be monitored in a minimal invasive manner. Blood-borne miRNAs are therefore currently characterized to identify, describe and va... |
Web-based NGS data analysis using miRMaster: a large-scale meta-analysis of human miRNAs Tobias Fehlmann, Christina Backes, Mustafa Kahraman, Jan Haas, Nicole Ludwig, Andreas E. Posch, Maximilian L. Würstle, Matthias Hübenthal, Andre Franke, Benjamin Meder, Eckart Meese, Andreas Keller The analysis of small RNA NGS data together with the discovery of new small RNAs is among the foremost challenges in life science. For the analysis of raw high-throughput sequencing data we implemented the fast, accurate and comprehensive web-based tool miRMaster. Our toolbox provides a wide range of modules for qua... |