Biology subjects

Del-Bem, L.-E.

Publications and source records attributed to Del-Bem, L.-E..

3 recordsLinked to original sources

bioRxiv2023

SARS-CoV-2 selectively induces the expression of unproductive splicing isoforms of interferon, class I MHC and splicing machinery genes

Splicing is a highly conserved, intricate mechanism intimately linked to transcription elongation, serving as a pivotal regulator of gene expression. Alternative splicing may generate specific transcripts incapable of undergoing translation into proteins, designated as unproductive. A plethora of respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), strategically manipulate the hosts splicing machinery to circumvent antiviral responses. During the infection, SARS-CoV-2 effectively suppresses interferon (IFN) expression, leading to B cell and CD8+ T cell leukopenia, while simultaneously increasing the presence of macrophages and neutrophils in patients with severe COVID-19. In this study, we integrated publicly available omics datasets to systematically analyze transcripts at the isoform level and delineate the nascent-peptide translatome landscapes of SARS-CoV-2-infected human cells. Our findings reveal a hitherto uncharacterized mechanism whereby SARS-CoV-2 infection induces the predominant expression of unproductive splicing isoforms in key IFN signaling genes, interferon-stimulated genes (ISGs), class I MHC genes, and splicing machinery genes, including IRF7, OAS3, HLA-B, and HNRNPH1. In stark contrast, cytokine and chemokine genes, such as IL6, CXCL8, and TNF, predominantly express productive (protein-coding) splicing isoforms in response to SARS-CoV-2 infection. We postulate that SARS-CoV-2 employs a previously unreported tactic of exploiting the host splicing machinery to bolster viral replication and subvert the immune response by selectively upregulating unproductive splicing isoforms from antigen presentation and antiviral response genes. Our study sheds new light on the molecular interplay between SARS-CoV-2 and the host immune system, offering a foundation for the development of novel therapeutic strategies to combat COVID-19.

bioinformatics↗

bioRxiv2022

Using ARCADE (ARChaeplastida Annotation DatabasE) to understand the evolution of genome size in land plants

The abundance of plant genomic information caused by the decrease of sequencing costs contrasts with the lack of databases that integrate genome annotation, taxonomy and phenotypes to produce statistically sound, biologically meaningful knowledge. Here we present ARCADE (ARChaeplastida Annotation DatabasE), a database of 171 high-quality archaeplastidian non-redundant proteomes gathered from six primary genomic databases, together with proteome quality metrics anda growing number of associated metadata. As a case study to demonstrate the usefulness of ARCADE, we used it to investigate the expansion and contraction of protein domains associated with the evolution of genome size (hereafter GS). GS varies greatly among land plants and the synthesis of large genomes can be costly to cells. Although GS has been studied extensively for decades, the molecular mechanisms involved in the adaptations of plants to the increase in GS are still poorly understood. We used the annotation and phylogenetic information available in ARCADE, together with estimated GS values available for 83 land plant species, to search for associations between the abundance of protein domain families in these species and GS variation through phylogenetic-aware methods. Additionally, we estimated the GS for the ancestral nodes of the extant land plant species. GS seems to be decreasing along the course of evolution, except for a few branches that might have undergone independent GS increases. We found 7 Pfam correlated with the variation in GS in land plants, mainly related to nucleotide metabolism, DNA repair and genome organization. We found larger genomes to have a greater frequency of the Histone 2A superfamily, responsible for diverse functions, including the nucleosome formation and silencing of transposable elements. These molecular functions we found correlated to GS variation suggests they may be associated with preserving genome stability in larger genomes, and might indicate the evolution of mechanisms to cope with the variation in GS in land plants. ARCADE is available at https://bit.ly/ARCADE_OSF.

plant biology↗

bioRxiv2022

Ferrous iron uptake via IRT1/ZIP evolved at least twice in green plants

Iron (Fe) is an essential micronutrient for virtually all living beings, being practically irreplaceable because of its unique electrochemical properties that enable or facilitate a series of biochemical processes, including photosynthesis. Although Fe is abundant on Earth, it is generally found in the poorly soluble form Fe3+. Most extant plants have established Fe absorption strategies that involve Fe uptake in the soluble form Fe2+. The model angiosperm Arabidopsis thaliana, for example, captures Fe through a mechanism that lowers the pH through proton pumping to the rhizosphere to increase Fe3+ solubility, which is then reduced by a plasma membrane-bound reductase and transported into the cell by the ZIP family protein IRT1. ZIP proteins are transmembrane transporters of a variety of divalent metals such as Fe2+, Zn2+, Mn2+ and Cd2+. In this work, we investigate the evolution of functional homologs of IRT1/ZIP in the supergroup of photosynthetic eukaryotes Archaeplastida (Viridiplantae + Rhodophyta + Glaucophyta) using a dataset of 41 high-quality genomes of diverse lineages. Our analyses suggest that Fe is acquired through deeply divergent ZIP proteins in land plants and chlorophyte green algae, indicating that Fe2+ uptake by ZIP family proteins evolved at least twice independently during green plant evolution. Sequence and structural analyses indicate that the archetypical IRT proteins from angiosperms likely emerged in streptophyte algae before the origin of land plants and might be an important player in green plant terrestrialization, a process that involved the evolution of Fe acquisition in terrestrial subaerial settings.

genomics↗