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Seminars in Cell & Developmental Biology Feb 2023The nucleolus is a large nuclear membraneless organelle responsible for ribosome biogenesis. Ribosomes are cytoplasmic macromolecular complexes comprising RNA and... (Review)
Review
The nucleolus is a large nuclear membraneless organelle responsible for ribosome biogenesis. Ribosomes are cytoplasmic macromolecular complexes comprising RNA and proteins that link amino acids together to form new proteins. The biogenesis of ribosomes is an intricate multistep process that involves the transcription of ribosomal DNA (rDNA), the processing of ribosomal RNA (rRNA), and the assembly of rRNA with ribosomal proteins to form active ribosomes. Nearly all steps necessary for ribosome production and maturation occur in the nucleolus. Nucleolar shape, size, and number are directly linked to ribosome biogenesis. Errors in the steps of ribosomal biogenesis are sensed by the nucleolus causing global alterations in nucleolar function and morphology. This phenomenon, known as nucleolar stress, can lead to molecular changes such as stabilization of p53, which in turn activates cell cycle arrest or apoptosis. In this review, we discuss recent work on the association of nucleolar stress with degenerative diseases and developmental defects. In addition, we highlight the importance of de novo nucleotide biosynthesis for the enhanced nucleolar activity of cancer cells and discuss targeting nucleotide biosynthesis as a strategy to activate nucleolar stress to specifically target cancer cells.
Topics: Humans; Cell Nucleolus; Ribosomes; Ribosomal Proteins; RNA, Ribosomal; Neoplasms; Nucleotides
PubMed: 35410715
DOI: 10.1016/j.semcdb.2022.04.001 -
Biomolecules Apr 2021The gut microbiome is a microbial ecosystem which expresses 100 times more genes than the human host and plays an essential role in human health and disease... (Review)
Review
The gut microbiome is a microbial ecosystem which expresses 100 times more genes than the human host and plays an essential role in human health and disease pathogenesis. Since most intestinal microbial species are difficult to culture, next generation sequencing technologies have been widely applied to study the gut microbiome, including 16S rRNA, 18S rRNA, internal transcribed spacer (ITS) sequencing, shotgun metagenomic sequencing, metatranscriptomic sequencing and viromic sequencing. Various software tools were developed to analyze different sequencing data. In this review, we summarize commonly used computational tools for gut microbiome data analysis, which extended our understanding of the gut microbiome in health and diseases.
Topics: Bacteria; Computational Biology; Fungi; Gastrointestinal Microbiome; High-Throughput Nucleotide Sequencing; Humans; RNA, Ribosomal, 16S; RNA, Ribosomal, 18S; Viruses
PubMed: 33918473
DOI: 10.3390/biom11040530 -
Biochemistry. Biokhimiia Jan 2018This review is focused on the structural aspects of interaction between ribosomal proteins and ribosomal RNA in bacterial ribosomes and complexes of ribosomal proteins... (Review)
Review
This review is focused on the structural aspects of interaction between ribosomal proteins and ribosomal RNA in bacterial ribosomes and complexes of ribosomal proteins with specific fragments of ribosomal RNA. Special attention is given to the recognition of specific spatial architecture of the double-stranded ribosomal RNA by ribosomal proteins and to the role of unstructured protein regions in stabilization of distant ribosomal RNA segments.
Topics: Protein Conformation; RNA, Ribosomal; Ribosomal Proteins
PubMed: 29544435
DOI: 10.1134/S0006297918140109 -
BMC Bioinformatics Aug 2021The DNA sequences encoding ribosomal RNA genes (rRNAs) are commonly used as markers to identify species, including in metagenomics samples that may combine many...
BACKGROUND
The DNA sequences encoding ribosomal RNA genes (rRNAs) are commonly used as markers to identify species, including in metagenomics samples that may combine many organismal communities. The 16S small subunit ribosomal RNA (SSU rRNA) gene is typically used to identify bacterial and archaeal species. The nuclear 18S SSU rRNA gene, and 28S large subunit (LSU) rRNA gene have been used as DNA barcodes and for phylogenetic studies in different eukaryote taxonomic groups. Because of their popularity, the National Center for Biotechnology Information (NCBI) receives a disproportionate number of rRNA sequence submissions and BLAST queries. These sequences vary in quality, length, origin (nuclear, mitochondria, plastid), and organism source and can represent any region of the ribosomal cistron.
RESULTS
To improve the timely verification of quality, origin and loci boundaries, we developed Ribovore, a software package for sequence analysis of rRNA sequences. The ribotyper and ribosensor programs are used to validate incoming sequences of bacterial and archaeal SSU rRNA. The ribodbmaker program is used to create high-quality datasets of rRNAs from different taxonomic groups. Key algorithmic steps include comparing candidate sequences against rRNA sequence profile hidden Markov models (HMMs) and covariance models of rRNA sequence and secondary-structure conservation, as well as other tests. Nine freely available blastn rRNA databases created and maintained with Ribovore are used for checking incoming GenBank submissions and used by the blastn browser interface at NCBI. Since 2018, Ribovore has been used to analyze more than 50 million prokaryotic SSU rRNA sequences submitted to GenBank, and to select at least 10,435 fungal rRNA RefSeq records from type material of 8350 taxa.
CONCLUSION
Ribovore combines single-sequence and profile-based methods to improve GenBank processing and analysis of rRNA sequences. It is a standalone, portable, and extensible software package for the alignment, classification and validation of rRNA sequences. Researchers planning on submitting SSU rRNA sequences to GenBank are encouraged to download and use Ribovore to analyze their sequences prior to submission to determine which sequences are likely to be automatically accepted into GenBank.
Topics: DNA, Ribosomal; Databases, Nucleic Acid; Phylogeny; RNA, Ribosomal; RNA, Ribosomal, 16S; RNA, Ribosomal, 18S; Sequence Analysis, RNA
PubMed: 34384346
DOI: 10.1186/s12859-021-04316-z -
Proceedings of the Japan Academy.... 2014The ribosomal RNA gene (rDNA) repeats form a historically well-researched region in the chromosome. Their highly repetitive structure can be identified easily which has... (Review)
Review
The ribosomal RNA gene (rDNA) repeats form a historically well-researched region in the chromosome. Their highly repetitive structure can be identified easily which has enabled studies on DNA replication, recombination, and transcription. The region is one of the most unstable regions in the genome because of deleterious recombination among the repeats. The ribosomal RNA gene repeats use a unique gene amplification system to restore the copy number after this has been reduced due to recombination. It has been shown that unstable features in the genome can accelerate cellular senescence that restricts the lifespan of a cell. Here, I will introduce a study by our group that shows how the stability of rDNA is maintained and affects lifespan. I propose that the ribosomal RNA gene repeats constitute a center from which the stability of the whole genome is regulated and the lifespan of the cell is controlled.
Topics: Animals; Cellular Senescence; DNA, Ribosomal; Genes, rRNA; Humans; RNA Stability; RNA, Ribosomal; Repetitive Sequences, Nucleic Acid
PubMed: 24727936
DOI: 10.2183/pjab.90.119 -
Biomolecules Oct 2018Ribosomal RNAs, the most abundant cellular RNA species, have evolved as the structural scaffold and the catalytic center of protein synthesis in every living organism.... (Review)
Review
Ribosomal RNAs, the most abundant cellular RNA species, have evolved as the structural scaffold and the catalytic center of protein synthesis in every living organism. In eukaryotes, they are produced from a long primary transcript through an intricate sequence of processing steps that include RNA cleavage and folding and nucleotide modification. The mechanisms underlying this process in human cells have long been investigated, but technological advances have accelerated their study in the past decade. In addition, the association of congenital diseases to defects in ribosome synthesis has highlighted the central place of ribosomal RNA maturation in cell physiology regulation and broadened the interest in these mechanisms. Here, we give an overview of the current knowledge of pre-ribosomal RNA processing in human cells in light of recent progress and discuss how dysfunction of this pathway may contribute to the physiopathology of congenital diseases.
Topics: Disease; Humans; Nucleic Acid Conformation; RNA Processing, Post-Transcriptional; RNA, Ribosomal; Ribosomal Proteins; Ribosomes
PubMed: 30356013
DOI: 10.3390/biom8040123 -
Trends in Biochemical Sciences Jul 2023The mitochondrial ribosome (mitoribosome) is a multicomponent machine that has unique structural features. Biogenesis of the human mitoribosome includes correct... (Review)
Review
The mitochondrial ribosome (mitoribosome) is a multicomponent machine that has unique structural features. Biogenesis of the human mitoribosome includes correct maturation and folding of the mitochondria-encoded RNA components (12S and 16S mt-rRNAs, and mt-tRNAVal) and their assembly together with 82 nucleus-encoded mitoribosomal proteins. This complex process requires the coordinated action of multiple assembly factors. Recent advances in single-particle cryo-electron microscopy (cryo-EM) have provided detailed insights into the specific functions of several mitoribosome assembly factors and have defined their timing. In this review we summarize mitoribosomal small (mtSSU) and large subunit (mtLSU) biogenesis based on structural findings, and we discuss potential crosstalk between mtSSU and mtLSU assembly pathways as well as coordination between mitoribosome biogenesis and other processes involved in mitochondrial gene expression.
Topics: Humans; Cryoelectron Microscopy; Mitochondrial Ribosomes; RNA, Ribosomal, 16S; Mitochondrial Proteins; Ribosomal Proteins
PubMed: 37169615
DOI: 10.1016/j.tibs.2023.04.002 -
Nucleic Acids Research 2007Five nearly universal methylated guanine-(N2) residues are present in bacterial rRNA in the ribosome. To date four out of five ribosomal RNA... (Review)
Review
Five nearly universal methylated guanine-(N2) residues are present in bacterial rRNA in the ribosome. To date four out of five ribosomal RNA guanine-(N2)-methyltransferases are described. RsmC(YjjT) methylates G1207 of the 16S rRNA. RlmG(YgjO) and RlmL(YcbY) are responsible for the 23S rRNA m(2)G1835 and m(2)G2445 formation, correspondingly. RsmD(YhhF) is necessary for methylation of G966 residue of 16S rRNA. Structure of Escherichia coli RsmD(YhhF) methyltransferase and the structure of the Methanococcus jannaschii RsmC ortholog were determined. All ribosomal guanine-(N2)-methyltransferases have similar AdoMet-binding sites. In relation to the ribosomal substrate recognition, two enzymes that recognize assembled subunits are relatively small single domain proteins and two enzymes that recognize naked rRNA are larger proteins containing separate methyltransferase- and RNA-binding domains. The model for recognition of specific target nucleotide is proposed. The hypothetical role of the m(2)G residues in rRNA is discussed.
Topics: Bacteria; Guanine; Methyltransferases; RNA, Ribosomal; Substrate Specificity
PubMed: 17389639
DOI: 10.1093/nar/gkm104 -
RNA (New York, N.Y.) Dec 2009Ribosome assembly is required for cell growth in all organisms. Classic in vitro work in bacteria has led to a detailed understanding of the biophysical, thermodynamic,... (Review)
Review
Ribosome assembly is required for cell growth in all organisms. Classic in vitro work in bacteria has led to a detailed understanding of the biophysical, thermodynamic, and structural basis for the ordered and correct assembly of ribosomal proteins on ribosomal RNA. Furthermore, it has enabled reconstitution of active subunits from ribosomal RNA and proteins in vitro. Nevertheless, recent work has shown that eukaryotic ribosome assembly requires a large macromolecular machinery in vivo. Many of these assembly factors such as ATPases, GTPases, and kinases hydrolyze nucleotide triphosphates. Because these enzymes are likely regulatory proteins, much work to date has focused on understanding their role in the assembly process. Here, we review these factors, as well as other sources of energy, and their roles in the ribosome assembly process. In addition, we propose roles of energy-releasing enzymes in the assembly process, to explain why energy is used for a process that occurs largely spontaneously in bacteria. Finally, we use literature data to suggest testable models for how these enzymes could be used as targets for regulation of ribosome assembly.
Topics: Animals; Humans; Nucleic Acid Conformation; Protein Multimerization; RNA, Ribosomal; Ribosomal Proteins; Ribosomes
PubMed: 19850913
DOI: 10.1261/rna.1792109 -
Cells Nov 2019The ribosome is a complex ribonucleoprotein-based molecular machine that orchestrates protein synthesis in the cell. Both ribosomal RNA and ribosomal proteins can be... (Review)
Review
The ribosome is a complex ribonucleoprotein-based molecular machine that orchestrates protein synthesis in the cell. Both ribosomal RNA and ribosomal proteins can be chemically modified by reactive oxygen species, which may alter the ribosome's functions or cause a complete loss of functionality. The oxidative damage that ribosomes accumulate during their lifespan in a cell may lead to reduced or faulty translation and contribute to various pathologies. However, remarkably little is known about the biological consequences of oxidative damage to the ribosome. Here, we provide a concise summary of the known types of changes induced by reactive oxygen species in rRNA and ribosomal proteins and discuss the existing experimental evidence of how these modifications may affect ribosome dynamics and function. We emphasize the special role that redox-active transition metals, such as iron, play in ribosome homeostasis and stability. We also discuss the hypothesis that redox-mediated ribosome modifications may contribute to adaptive cellular responses to stress.
Topics: Animals; Homeostasis; Humans; Iron; Oxidation-Reduction; Oxidative Stress; Protein Biosynthesis; RNA, Ribosomal; Reactive Oxygen Species; Ribosomes
PubMed: 31684095
DOI: 10.3390/cells8111379