rna fragments
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2022 ◽  
Author(s):  
Tamara Zorbaz ◽  
Nimrod Madrer ◽  
Hermona Soreq

Inflammatory stimuli and consequent pro-inflammatory immune responses may facilitate neurodegeneration and threaten survival following pathogen infection or trauma, but potential controllers preventing these risks are incompletely understood. Here, we argue that small RNA regulators of acetylcholine (ACh) signaling, including microRNAs and transfer RNA fragments may tilt the balance between innate and adaptive immunity, avoid chronic inflammation and prevent the neuroinflammation-mediated exacerbation of many neurological diseases. While the restrictive permeability of the blood-brain barrier protects the brain from peripheral immune events, this barrier can be disrupted by inflammation and is weakened with age. The consequently dysregulated balance between pro- and anti-inflammatory processes may modify the immune activities of brain microglia, astrocytes, perivascular macrophages, oligodendrocytes and dendritic cells, leading to neuronal damage. Notably, the vagus nerve mediates the peripheral cholinergic anti-inflammatory reflex and underlines the consistent control of body-brain inflammation by pro-inflammatory cytokines, which affect cholinergic functions; therefore, the disruption of this reflex can exacerbate cognitive impairments such as attention deficits and delirium. RNA regulators can contribute to re-balancing the cholinergic network and avoiding its chronic deterioration, and their activities may differ between men and women and/or wear off with age. This can lead to hypersensitivity of aged patients to inflammation and higher risks of neuroinflammatory-driven cholinergic impairments such as delirium and dementia following COVID-19 infection. The age- and sex-driven differences in post-transcriptional RNA regulators of cholinergic elements may hence indicate new personalized therapeutic options for neuroinflammatory diseases.


2021 ◽  
Vol 9 (12) ◽  
pp. 108-132
Author(s):  
Jean Claude Perez ◽  
Valère Lounnas ◽  
Montagnier Montagnier

We analyze here 7 very first strains of OMICRON the SARS-CoV2 new variant from South Africa, the USA (California and Minesota), Canada and Belgium. We applied, at the scale of the whole genome and the spike gene, the biomathematics method of Fibonacci meta-structure fractal analysis applied to the UA / CG proportions.  We have evidenced the RUPTURE of OMICRON with respect to ALL the previous variants: D614G, ALPHA, BETA, GAMMA, DELTA. Remarkably, it is observed that the density of OMICRON mutations in the SPIKE PRION region is more than 8 times that of the rest of the Spike protein. In particular, we suggest that the mRNA stabilizing secondary structure ("hairpin" conformation) in the spike of all variants is degraded in OMICRON, probably making its mRNA more fragile. The loss of long-range fractal meta-structures in the OMICRON spike gene are in line with common knowledge on the mechanisms of epidemic ending, involving  recombination of heavily mutated RNA fragments of the virus, with the possible inference of a distinct helper virus. This would indicate that the SARS-CoV2 is under very strong evolutionary pressure,  possibly marking the end of the pandemic. We are studying more particularly the prion-like region of the spike, the mutations rate of which is 8 times higher in OMICRON than that of the whole spike protein.


2021 ◽  
Author(s):  
Yang-Ming Yeh ◽  
Yi-Chang Lu

MinION, a third-generation sequencer from Oxford Nanopore Technologies, is a portable device that can provide long nucleotide read data in real-time. It primarily aims to deduce the makeup of nucleotide sequences from the ionic current signals generated when passing DNA/RNA fragments through nanopores charged with a voltage difference. To determine the nucleotides from the measured signals, a translation process known as basecalling is required. However, compared to NGS basecallers, the calling accuracy of MinION still needs to be improved. In this work, a simple but powerful neural network architecture called MSRCall is proposed. MSRCall comprises a multi-scale structure, recurrent layers, a fusion block, and a CTC decoder. To better identify both short-range and long-range dependencies, the recurrent layer is redesigned to capture various time-scale features with a multi-scale structure. The results show that MSRCall outperforms other basecallers in terms of both read and consensus accuracies.


2021 ◽  
Vol 5 (3) ◽  
pp. e202101240
Author(s):  
Shoeb Ikhlas ◽  
Afia Usman ◽  
Dongkyeong Kim ◽  
Dongsheng Cai

Murine neural stem cells (NSCs) were recently shown to release piRNA-containing exosomes/microvesicles (Ex/Mv) for exerting antiviral immunity, but it remains unknown if these Ex/Mv could target SARS-CoV-2 and whether the PIWI-piRNA system is important for these antiviral actions. Here, using in vitro infection models, we show that hypothalamic NSCs (htNSCs) Ex/Mv provided an innate immunity protection against SARS-CoV-2. Importantly, enhanced antiviral actions were achieved by using induced Ex/Mv that were derived from induced htNSCs through twice being exposed to several RNA fragments of SARS-CoV-2 genome, a process that was designed not to involve protein translation of these RNA fragments. The increased antiviral effects of these induced Ex/Mv were associated with increased expression of piRNA species some of which could predictably target SARS-CoV-2 genome. Knockout of piRNA-interacting protein PIWIL2 in htNSCs led to reductions in both innate and induced antiviral effects of Ex/Mv in targeting SARS-CoV-2. Taken together, this study demonstrates a case suggesting Ex/Mv from certain cell types have innate and adaptive immunity against SARS-CoV-2, and the PIWI-piRNA system is important for these antiviral actions.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Florent Waltz ◽  
Thalia Salinas-Giegé ◽  
Robert Englmeier ◽  
Herrade Meichel ◽  
Heddy Soufari ◽  
...  

AbstractMitochondria are the powerhouse of eukaryotic cells. They possess their own gene expression machineries where highly divergent and specialized ribosomes, named hereafter mitoribosomes, translate the few essential messenger RNAs still encoded by mitochondrial genomes. Here, we present a biochemical and structural characterization of the mitoribosome in the model green alga Chlamydomonas reinhardtii, as well as a functional study of some of its specific components. Single particle cryo-electron microscopy resolves how the Chlamydomonas mitoribosome is assembled from 13 rRNA fragments encoded by separate non-contiguous gene pieces. Additional proteins, mainly OPR, PPR and mTERF helical repeat proteins, are found in Chlamydomonas mitoribosome, revealing the structure of an OPR protein in complex with its RNA binding partner. Targeted amiRNA silencing indicates that these ribosomal proteins are required for mitoribosome integrity. Finally, we use cryo-electron tomography to show that Chlamydomonas mitoribosomes are attached to the inner mitochondrial membrane via two contact points mediated by Chlamydomonas-specific proteins. Our study expands our understanding of mitoribosome diversity and the various strategies these specialized molecular machines adopt for membrane tethering.


2021 ◽  
Author(s):  
Lydia Herzel ◽  
Julian A Stanley ◽  
James C Taggart ◽  
Gene-Wei LI

Bacterial mRNAs have short life cycles, in which transcription is rapidly followed by translation and degradation within seconds to minutes. The resulting diversity of mRNAs impacts their functionality but has remained unresolved. Here we quantitatively map the 3' status of cellular RNAs in Escherichia coli during steady-state growth and report a large fraction of molecules (median>60%) that are fragments of canonical full-length mRNAs. The majority of RNA fragments are decay intermediates following endonuclease cleavage by RNase E and yet-unknown nucleases, whereas nascent RNAs contribute to a smaller fraction. Despite the prevalence of decay intermediates in total RNA, they are underrepresented in the pool of ribosome-associated transcripts and can thus distort quantifications for the abundance of full-length, functional mRNAs. The large heterogeneity within mRNA molecules in vivo highlights the importance in discerning functional transcripts and provides a lens for studying the dynamic life cycle of mRNAs.


2021 ◽  
Vol 2099 (1) ◽  
pp. 012037
Author(s):  
N S Kobalo ◽  
A A Kulikov ◽  
I I Titov

Abstract The pandemic of the coronavirus infection COVID-19, which began at the end of 2019 and caused by the SARS-CoV-2 virus, has led to unprecedented consequences in the world. By the end of May 2021, in the world there were 167 million infected and 3.5 million died directly from infection [1]. SARS-CoV-2 is a beta coronavirus, so it shares many conserved fragments with other known viruses of this type [2]. Since the beginning of the spread of the COVID-19, one of the important issues of research of the SARS-CoV-2 virus has been the search for its conserved RNA motifs and their functional annotation. These motifs are potential targets for the treatment and diagnosis of a disease caused by the virus. This report examines the structural RNA fragments of SARS-CoV-2, similar to the corresponding fragments in other beta coronaviruses [2]. For these RNA motifs the nucleotide variability during the spread of the virus, depending on their secondary structure, was investigated. All the motifs display the similar background variability although contain hypervariable positions.


2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Nicole Farfán ◽  
Nicole Sanhueza ◽  
Macarena Briones ◽  
Luis O. Burzio ◽  
Verónica A. Burzio

Abstract Background The antisense noncoding mitochondrial RNAs (ASncmtRNAs) derive from the mitochondrial 16S gene. Knockdown of these transcripts with chemically-modified antisense oligonucleotides induces proliferative arrest, apoptosis and invasiveness reduction in tumor but not normal cells. One of these transcripts, ASncmtRNA-2, contains the complete and identical sequence of hsa-miR-4485-3p and, upon knockdown of this transcript, there is a strong increase in levels of this miRNA, suggesting ASncmtRNA-2 as a source for miR-4485-3p, which is supported by several evidences from our group and others, in the ex vivo setting. Results Here we show that incubation of in vitro-transcribed ASncmtRNA-2 with recombinant Dicer produces RNA fragments corresponding to hsa-miR-4485-3p, showing that Dicer binds to and processes ASncmtRNA-2, strongly supporting the hypothesis that ASncmtRNA-2 acts as a precursor for miR-4485-3p. Conclusion The in vitro results presented here strengthen the hypothesis that miR-4485-3p is derived from ASncmtRNA-2 by Dicer processing. Since miR-4485-3p is classified as a tumor suppressor miRNA, this evidence strengthens the application of ASncmtRNA knockdown for cancer therapy.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Hyun Jin Yoo ◽  
Yun Guang Li ◽  
Wen Ying Cui ◽  
Wonseok Chung ◽  
Yong-Beom Shin ◽  
...  

AbstractIt is highly important to sensitively measure the abundance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on various surfaces. Here, we present a nucleic acid-based detection method consisting of a new sample preparation protocol that isolates only viruses, not the free RNA fragments already present on the surfaces of indoor human-inhabited environments, using a graphene oxide-coated microbead filter. Wet wipes (100 cm2), not cotton swabs, were used to collect viruses from environmental surfaces with large areas, and viruses were concentrated and separated with a graphene oxide-coated microbead filter. Viral RNA from virus was recovered 88.10 ± 8.03% from the surface and free RNA fragment was removed by 99.75 ± 0.19% from the final eluted solution. When we tested the developed method under laboratory conditions, a 10-fold higher viral detection sensitivity (Detection limit: 1 pfu/100 cm2) than the current commercial protocol was observed. Using our new sample preparation protocol, we also confirmed that the virus was effectively removed from surfaces after chemical disinfection; we were unable to measure the disinfection efficiency using the current commercial protocol because it cannot distinguish between viral RNA and free RNA fragments. Finally, we investigated the presence of SARS-CoV-2 and bacteria in 12 individual negative pressure wards in which patients with SARS-CoV-2 infection had been hospitalized. Bacteria (based on 16 S DNA) were found in all samples collected from patient rooms; however, SARS-CoV-2 was mainly detected in rooms shared by two patients.


2021 ◽  
Vol 22 (20) ◽  
pp. 11014
Author(s):  
Ryoma Yoneda ◽  
Naomi Ueda ◽  
Riki Kurokawa

Translocated in LipoSarcoma/Fused in Sarcoma (TLS/FUS) is a nuclear RNA binding protein whose mutations cause amyotrophic lateral sclerosis. TLS/FUS undergoes LLPS and forms membraneless particles with other proteins and nucleic acids. Interaction with RNA alters conformation of TLS/FUS, which affects binding with proteins, but the effect of m6A RNA modification on the TLS/FUS–RNA interaction remains elusive. Here, we investigated the binding specificity of TLS/FUS to m6A RNA fragments by RNA pull down assay, and elucidated that both wild type and ALS-related TLS/FUS mutants strongly bound to m6A modified RNAs. TLS/FUS formed cytoplasmic foci by treating hyperosmotic stress, but the cells transfected with m6A-modified RNAs had a smaller number of foci. Moreover, m6A-modified RNA transfection resulted in the cells obtaining higher resistance to the stress. In summary, we propose TLS/FUS as a novel candidate of m6A recognition protein, and m6A-modified RNA fragments diffuse cytoplasmic TLS/FUS foci and thereby enhance cell viability.


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