Chapters authored
Mammalian Cis-Acting RNA Sequence Elements By Irina Vlasova-St. Louis and Calandra Sagarsky
Cis-acting regulatory sequence elements are sequences contained in the 3′ and 5′ untranslated region, introns, or coding regions of precursor RNAs and mature mRNAs that are selectively recognized by a complementary set of one or more trans-acting factors to regulate posttranscriptional gene expression. This chapter focuses on mammalian cis-acting regulatory elements that had been recently discovered in different regions: pre-processed and mature. The chapter begins with an overview of two large networks of mRNAs that contain conserved AU-rich elements (AREs) or GU-rich elements (GREs), and their role in mammalian cell physiology. Other, less conserved, cis-acting elements and their functional role in different steps of RNA maturation and metabolism will be discussed. The molecular characteristics of pathological cis-acting sequences that rose from gene mutations or transcriptional aberrations are briefly outlined, with the proposed approach to restore normal gene expression. Concise models of the function of posttranscriptional regulatory networks within different cellular compartments conclude this chapter.
Part of the book: Gene Expression and Regulation in Mammalian Cells
Diagnostic Applications for RNA-Seq Technology and Transcriptome Analyses in Human Diseases Caused by RNA Viruses By Irina Vlasova-St. Louis, Andrew Gorzalski and Mark Pandori
Human diseases caused by single-stranded, positive-sense RNA viruses, are among the deadliest of the 21st Century. In particular, there are two notable standouts: human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Detection of these disease-causing viral transcripts, by next-generation RNA sequencing (RNA-Seq), represents the most immediate opportunity for advances in diagnostic, therapeutic, and preventive applicability in infectious diseases (e.g., AIDS and COVID-19). Moreover, RNA-Seq technologies add significant value to public health studies by first, providing real-time surveillance of known viral strains, and second, by the augmentation of epidemiological databases, construction of annotations and classifications of novel sequence variants. This chapter intends to recapitulate the current knowledge of HIV and SARS-CoV-2 transcriptome architecture, pathogenicity, and some features of the host immune response. Additionally, it provides an overview of recent advances in diagnostic sequencing methodologies and discusses the future challenges and prospects on the utilization of RNA-Seq technologies.
Part of the book: Applications of RNA-Seq in Biology and Medicine
Prophylactic Ribonucleic Acid Vaccines to Combat RNA Viral Infections in Humans By Irina Vlasova-St. Louis and Jude Abadie
Vaccines have evolved as widely applicable and available prophylaxes against infectious diseases. Advances in ribonucleic acid technologies revolutionized the biopharmaceutical field of vaccine manufacturing. Numerous novel mRNA-based vaccines that have been approved by the United States and European regulatory agencies are proven to be safe and effective in preventing disease. This chapter presents the history of RNA vaccine development in the context of preventing diseases caused by RNA viruses such as SARS-CoV-2, HIV, influenza, Chikungunya, Zika, RSV, PIV, HMPV viruses, Rabies, and Ebola. Advantages, disadvantages, and challenges in mRNA vaccine engineering, delivery, and safety are discussed. The formulation, safety, long-term effectiveness, and requirements for booster immunizations are presented using data from clinical trials. The results of these clinical trials highlight important milestones, setbacks, and ultimate advancements in vaccine development. mRNA vaccines have significantly impacted public health in a relatively short time, and they demonstrate great potential in serving as clinical public health prophylaxis against current and future pandemics. Future development is likely to include polyvalent, mosaic, and strain/lineage-specific individualized vaccines.
Part of the book: RNA Therapeutics
Perspective Chapter: Next-Generation Sequencing and Variant Cataloging for Screening and Diagnosis of Sphingolipidoses and Mucopolysaccharidoses By Irina Vlasova-St. Louis, Uri Barak and Svetlana Khaiboullina
This chapter provides a comprehensive examination of how next-generation sequencing (NGS) technologies are transforming prenatal and neonatal care, particularly in the diagnosis of lysosomal diseases (LDs). These rare, inherited conditions are caused by defects in lysosomal metabolism. If not detected and treated early, they can lead to significant disabilities and reduced life expectancy. The chapter specifically focuses on the use of NGS to diagnose and screen sphingolipidoses (SLDs) and mucopolysaccharidoses (MPSs). It covers the molecular pathogenesis, classification, and main symptomatology of the diseases. The chapter reviews the progress made in identifying the genes associated with SLDs and MPSs and cataloging clinically relevant genetic variants. Additionally, it highlights the growing adoption of NGS for diagnosis and screening by institutions such as academic research centers, private healthcare providers, and government health agencies. It also discusses the challenges in NGS implementation, regulation, and outlines future directions for its application in prenatal and neonatal medicine.
Part of the book: Selected Topics in Prenatal and Neonatal Diagnoses
View all chapters
