Buffy Coat Transcriptomic Analysis Reveals Alterations in Host Cell Protein Synthesis and Cell Cycle in Severe COVID-19 Patients

Autor:	Liliane Tavares de Faria Cavalcante, Guilherme Cordenonsi da Fonseca, Luciane Almeida Amado Leon, Andreza Lemos Salvio, Otávio José Brustolini, Alexandra Lehmkuhl Gerber, Ana Paula de Campos Guimarães, Carla Augusta Barreto Marques, Renan Amphilophio Fernandes, Carlos Henrique Ferreira Ramos Filho, Rafael Lopes Kader, Marisa Pimentel Amaro, João Paulo da Costa Gonçalves, Soniza Vieira Alves-Leon, Ana Tereza Ribeiro Vasconcelos
Rok vydání:	2022
Předmět:	SARS-CoV-2 Gene Expression Profiling Organic Chemistry Cell Cycle COVID-19 General Medicine Catalysis Computer Science Applications Inorganic Chemistry Humans RNA Long Noncoding RNA-seq lncRNA biomarkers buffy coat FBL ICU patients Physical and Theoretical Chemistry Transcriptome Molecular Biology Spectroscopy
Zdroj:	International Journal of Molecular Sciences; Volume 23; Issue 21; Pages: 13588
ISSN:	1422-0067
Popis:	Transcriptome studies have reported the dysregulation of cell cycle-related genes and the global inhibition of host mRNA translation in COVID-19 cases. However, the key genes and cellular mechanisms that are most affected by the severe outcome of this disease remain unclear. For this work, the RNA-seq approach was used to study the differential expression in buffy coat cells of two groups of people infected with SARS-CoV-2: (a) Mild, with mild symptoms; and (b) SARS (Severe Acute Respiratory Syndrome), who were admitted to the intensive care unit with the severe COVID-19 outcome. Transcriptomic analysis revealed 1009 up-regulated and 501 down-regulated genes in the SARS group, with 10% of both being composed of long non-coding RNA. Ribosome and cell cycle pathways were enriched among down-regulated genes. The most connected proteins among the differentially expressed genes involved transport dysregulation, proteasome degradation, interferon response, cytokinesis failure, and host translation inhibition. Furthermore, interactome analysis showed Fibrillarin to be one of the key genes affected by SARS-CoV-2. This protein interacts directly with the N protein and long non-coding RNAs affecting transcription, translation, and ribosomal processes. This work reveals a group of dysregulated processes, including translation and cell cycle, as key pathways altered in severe COVID-19 outcomes.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d7d8c4981b317d5b1d5b21fc40f62499 https://pubmed.ncbi.nlm.nih.gov/36362378 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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