Biology subjects

Antoneli, F.

Publications and source records attributed to Antoneli, F..

3 recordsLinked to original sources

bioRxiv2025

SARS-CoV-2 reshapes mA methylation in long non-coding RNAs of human lung cells

N-Methyladenosine (mA) is a key base modification that regulates RNA stability and translation during viral infection. While mA methylation of host mRNAs has been studied in SARS-CoV-2-infected cells, its role in long non-coding RNAs (lncRNAs) is unknown. Here, we analyzed direct RNA sequencing (dRNA-seq) data from infected human lung cells (Calu-3) using a machine learning mA detection framework. We observed a global increase in mA levels across ten antiviral response- associated lncRNAs, with UCA1, GAS5, and NORAD--regulators of interferon (IFN) signaling-- showing the most pronounced changes. This might, in part, explain the attenuated IFN expression observed in infected cells. We identified methylated DRACH motifs in predicted lncRNA duplex-forming regions, which may favor Hoogsteen base-pairing, which destabilize secondary structures and target interaction sites. These results provide new perspectives on how SARS-CoV-2 could impact lncRNAs to modulate host immunity and viral persistence through mA-dependent mechanisms. In BriefPeter et al. show that SARS-CoV-2 infection alters mA methylation of host lncRNAs by analysis of direct RNA sequencing data with machine learning. Key immune-regulatory lncRNAs show mA alterations in RNA pairing regions, suggesting a novel mechanism by which mA may modulate antiviral responses and promote viral persistence. HighlightsO_LIDirect RNA-seq and machine learning reveal mA changes in lncRNAs C_LIO_LISARS-CoV-2 infection changes mA patterns in antiviral response-associated lncRNAs C_LIO_LILncRNAs UCA1, GAS5, and NORAD exhibit pronounced mA remodeling upon infection C_LIO_LImA sites overlap RNA duplex-forming regions in immune-regulatory lncRNAs C_LIO_LImA may impact lncRNA duplexes via Hoogsteen pairing C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=186 HEIGHT=200 SRC="FIGDIR/small/658496v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@eb2e28org.highwire.dtl.DTLVardef@236149org.highwire.dtl.DTLVardef@c82cd3org.highwire.dtl.DTLVardef@1f70f9e_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2021

Direct RNA sequencing reveals SARS-CoV-2 m6A sites and possible differential DRACH motif methylation among variants

The causative agent of COVID-19 pandemic, the SARS-CoV-2 coronavirus, has a 29,903 bases positive-sense single-stranded RNA genome. RNAs exhibit about 100 modified bases that are essential for proper function. Among internal modified bases, the N6-methyladenosine, or m6A, is the most frequent, and is implicated in SARS-CoV-2 immune response evasion. Although the SARS-CoV-2 genome is RNA, almost all genomes sequenced so far are in fact, reverse transcribed complementary DNAs. This process reduces the true complexity of these viral genomes because incorporation of dNTPs hides RNA base modifications. Here, in this perspective paper, we present an initial exploration of the Nanopore direct RNA sequencing to assess the m6A residues in the SARS-CoV-2 sequences of ORF3a, E, M, ORF6, ORF7a, ORF7b, ORF8, N, ORF10 and the 3-untranslated region. We identified 15 m6A methylated positions, of which, 6 are in ORF N. Also, because m6A is associated with the DRACH motif, we compared its distribution in major SARS-CoV-2 variants. Although DRACH is highly conserved among variants we show that variants Beta and Eta have a fourth position C>U change in DRACH at 28,884b that could affect methylation. The Nanopore technology offers a unique opportunity for the study of viral epitranscriptomics. This technique is PCR-free and is not sequencing-by-synthesis, therefore, no PCR bias and synthesis errors are introduced. The modified bases are preserved and assessed directly with no need for chemical treatments or antibodies. This is the first report of direct RNA sequencing of a Brazilian SARS-CoV-2 sample coupled with the identification of modified bases.

genomics↗

bioRxiv2018

Evolution of pathogenic and nonpathogenic yeasts mitochondrial genomes inferred by supertrees and supermatrices with divergence estimates based on relaxed molecular clocks

The evolution of mitochondrial genomes is essential for the adaptation of yeasts to the variation of environmental levels of oxygen. Although Saccharomyces cerevisiae mitochondrial DNA lacks all complex I genes, respiration is possible because alternative NADH dehydrogenases are encoded by NDE1 and NDI1 nuclear genes. The proposed whole genome duplication (WGD) in the yeast ancestor at 150-100 million years ago caused nuclear gene duplications and secondary losses, although its relation to the loss of complex I mitocondrial is unknown. Here we present phylogenomic supertrees and supermatrix tree of 46 mitochondrial genomes showing that the loss of complex I predates WGD and occurred independently in the S. cerevisiae group and the fission yeast Schizosaccharomyces pombe. We also show that the branching patterns do not differ dramatically in supertrees and supermatrix phylogenies. Our inferences indicated consistent relations between conserved mitochondrial chromosomal gene order (synteny) in closely related yeasts. Correlation of mitochondrial molecular clock estimates and atmospheric oxygen variation in the Phanerozoic suggests that the Saccharomyces lineage might have lost the complex I during hypoxic periods near Perminian-Triassic or Triassic-Jurassic mass extinction events, while the Schizosaccharomyces lineage possibly lost the complex I during hypoxic environment periods during Middle Cambrian until Lower Devonian. The loss of mitochondrial complex I during low oxygen might not affect yeast metabolism due to fermentative switch. The return to increased oxygen periods might have favored adaptations to aerobic metabolism. Additionally, we also showed that NDE1 and NDI1 phylogenies indicate evolutionary convergence in yeasts where mitochondrial complex I is absent.

genomics↗