Browsing by Author "Kellogg, Morgana K. (TTUHSC)"
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Item Pathogenic signal peptide variants in the human genome(2023) Guarnizo, Sneider Alexander Gutierrez (TTUHSC); Kellogg, Morgana K. (TTUHSC); Miller, Sarah C. (TTUHSC); Tikhonova, Elena B. (TTUHSC); Karamysheva, Zemfira N. (TTU); Karamyshev, Andrey L. (TTUHSC)Secreted and membrane proteins represent a third of all cellular proteins and contain N-terminal signal peptides that are required for protein targeting to endoplasmic reticulum (ER). Mutations in signal peptides affect protein targeting, translocation, processing, and stability, and are associated with human diseases. However, only a few of them have been identified or characterized. In this report, we identified pathogenic signal peptide variants across the human genome using bioinformatic analyses and predicted the molecular mechanisms of their pathology. We recovered more than 65 thousand signal peptide mutations, over 11 thousand we classified as pathogenic, and proposed framework for distinction of their molecular mechanisms. The pathogenic mutations affect over 3.3 thousand genes coding for secreted and membrane proteins. Most pathogenic mutations alter the signal peptide hydrophobic core, a critical recognition region for the signal recognition particle, potentially activating the Regulation of Aberrant Protein Production (RAPP) quality control and specific mRNA degradation. The remaining pathogenic variants (about 25%) alter either the N-terminal region or signal peptidase processing site that can result in translocation deficiencies at the ER membrane or inhibit protein processing. This work provides a conceptual framework for the identification of mutations across the genome and their connection with human disease.Item Ribosome Specialization in Protozoa Parasites(2023) Rodríguez-Almonacid, Cristian Camilo (TTU); Kellogg, Morgana K. (TTUHSC); Karamyshev, Andrey L. (TTUHSC); Karamysheva, Zemfira N. (TTU)Ribosomes, in general, are viewed as constitutive macromolecular machines where protein synthesis takes place; however, this view has been recently challenged, supporting the hypothesis of ribosome specialization and opening a completely new field of research. Recent studies have demonstrated that ribosomes are heterogenous in their nature and can provide another layer of gene expression control by regulating translation. Heterogeneities in ribosomal RNA and ribosomal proteins that compose them favor the selective translation of different sub-pools of mRNAs and functional specialization. In recent years, the heterogeneity and specialization of ribosomes have been widely reported in different eukaryotic study models; however, few reports on this topic have been made on protozoa and even less on protozoa parasites of medical importance. This review analyzes heterogeneities of ribosomes in protozoa parasites highlighting the specialization in their functions and their importance in parasitism, in the transition between stages in their life cycle, in the change of host and in response to environmental conditions.Item Specialized Ribosomes in Health and Disease(2023) Miller, Sarah C. (TTUHSC); MacDonald, Clinton C. (TTUHSC); Kellogg, Morgana K. (TTUHSC); Karamysheva, Zemfira N. (TTU); Karamyshev, Andrey L. (TTUHSC)Ribosomal heterogeneity exists within cells and between different cell types, at specific developmental stages, and occurs in response to environmental stimuli. Mounting evidence supports the existence of specialized ribosomes, or specific changes to the ribosome that regulate the translation of a specific group of transcripts. These alterations have been shown to affect the affinity of ribosomes for certain mRNAs or change the cotranslational folding of nascent polypeptides at the exit tunnel. The identification of specialized ribosomes requires evidence of the incorporation of different ribosomal proteins or of modifications to rRNA and/or protein that lead(s) to physiologically relevant changes in translation. In this review, we summarize ribosomal heterogeneity and specialization in mammals and discuss their relevance to several human diseases.