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Cold Spring Harbor Perspectives in... Jul 2011Pre-mRNA splicing is catalyzed by the spliceosome, a multimegadalton ribonucleoprotein (RNP) complex comprised of five snRNPs and numerous proteins. Intricate RNA-RNA... (Review)
Review
Pre-mRNA splicing is catalyzed by the spliceosome, a multimegadalton ribonucleoprotein (RNP) complex comprised of five snRNPs and numerous proteins. Intricate RNA-RNA and RNP networks, which serve to align the reactive groups of the pre-mRNA for catalysis, are formed and repeatedly rearranged during spliceosome assembly and catalysis. Both the conformation and composition of the spliceosome are highly dynamic, affording the splicing machinery its accuracy and flexibility, and these remarkable dynamics are largely conserved between yeast and metazoans. Because of its dynamic and complex nature, obtaining structural information about the spliceosome represents a major challenge. Electron microscopy has revealed the general morphology of several spliceosomal complexes and their snRNP subunits, and also the spatial arrangement of some of their components. X-ray and NMR studies have provided high resolution structure information about spliceosomal proteins alone or complexed with one or more binding partners. The extensive interplay of RNA and proteins in aligning the pre-mRNA's reactive groups, and the presence of both RNA and protein at the core of the splicing machinery, suggest that the spliceosome is an RNP enzyme. However, elucidation of the precise nature of the spliceosome's active site, awaits the generation of a high-resolution structure of its RNP core.
Topics: Catalytic Domain; Crystallography, X-Ray; Humans; Models, Genetic; Models, Molecular; Nuclear Magnetic Resonance, Biomolecular; Nucleic Acid Conformation; Protein Processing, Post-Translational; Protein Structure, Tertiary; RNA Precursors; RNA Splicing; Ribonucleoproteins; Ribonucleoproteins, Small Nuclear; Spliceosomes
PubMed: 21441581
DOI: 10.1101/cshperspect.a003707 -
Trends in Microbiology Mar 2023Influenza virus contains a single-stranded negative-sense RNA genome. Replication of the genome is carried out by the viral RNA-dependent RNA polymerase in the context... (Review)
Review
Influenza virus contains a single-stranded negative-sense RNA genome. Replication of the genome is carried out by the viral RNA-dependent RNA polymerase in the context of the viral ribonucleoprotein (RNP) complex, through a positive-sense complementary RNA intermediate. Genome replication is tightly controlled through interactions with accessory viral and host factors. Propelled by developments in recombinant protein expression, and technical improvements in X-ray crystallography and cryo-electron microscopy, snapshots of the replication process have been captured. Here, we review how recent structural data shed light on the molecular mechanisms of influenza virus genome replication, in particular, encapsidation of nascent RNA, de novo RNP assembly, and regulation of replication initiation through interactions with host and viral cues.
Topics: Humans; Ribonucleoproteins; Cryoelectron Microscopy; RNA, Viral; Virus Replication; Orthomyxoviridae; Influenza, Human
PubMed: 36336541
DOI: 10.1016/j.tim.2022.09.015 -
Genes & Development May 2023RNA granules are mesoscale assemblies that form in the absence of limiting membranes. RNA granules contain factors for RNA biogenesis and turnover and are often assumed... (Review)
Review
RNA granules are mesoscale assemblies that form in the absence of limiting membranes. RNA granules contain factors for RNA biogenesis and turnover and are often assumed to represent specialized compartments for RNA biochemistry. Recent evidence suggests that RNA granules assemble by phase separation of subsoluble ribonucleoprotein (RNP) complexes that partially demix from the cytoplasm or nucleoplasm. We explore the possibility that some RNA granules are nonessential condensation by-products that arise when RNP complexes exceed their solubility limit as a consequence of cellular activity, stress, or aging. We describe the use of evolutionary and mutational analyses and single-molecule techniques to distinguish functional RNA granules from "incidental condensates."
Topics: Ribonucleoproteins; Cytoplasmic Granules; Cytoplasmic Ribonucleoprotein Granules; RNA
PubMed: 37137715
DOI: 10.1101/gad.350518.123 -
Biological Chemistry Oct 2023
Topics: Protein Binding; Ribonucleoproteins
PubMed: 37768939
DOI: 10.1515/hsz-2023-0301 -
Structure (London, England : 1993) Jan 2020Ribonucleoprotein complexes (RNPs) are central to all processes in the cell. One of the prerequisites to understand how RNPs work is to determine their high-resolution... (Review)
Review
Ribonucleoprotein complexes (RNPs) are central to all processes in the cell. One of the prerequisites to understand how RNPs work is to determine their high-resolution structures. With the recent revolution in cryoelectron microscopy this task has become easier for large RNP machines, such as ribosomes, spliceosomes, and polymerases. However, the transient and highly dynamic nature of many RNPs makes structure determination a challenging task. Thus, an integrative structural and molecular biology approach is required, tackling three key challenges: (1) identification of cognate RNA sequences; (2) collection of structural data by conducting X-ray crystallography, NMR, electron microscopy, small-angle scattering (SAS), and other experiments; and (3) the creation of structural models that integrates all experimental restraints. Given the breadth of expertise required, this review presents an overview of available methods and successful examples with the goal to provide readers with a selection of promising options for structure determination of RNPs.
Topics: Base Sequence; Cryoelectron Microscopy; Crystallography, X-Ray; Models, Molecular; Ribonucleoproteins; Scattering, Small Angle
PubMed: 31864810
DOI: 10.1016/j.str.2019.11.017 -
Nature Cell Biology Apr 2022Biomolecular condensates organize biochemistry, yet little is known about how cells control the position and scale of these structures. In cells, condensates often...
Biomolecular condensates organize biochemistry, yet little is known about how cells control the position and scale of these structures. In cells, condensates often appear as relatively small assemblies that do not coarsen into a single droplet despite their propensity to fuse. Here, we report that ribonucleoprotein condensates of the glutamine-rich protein Whi3 interact with the endoplasmic reticulum, which prompted us to examine how membrane association controls condensate size. Reconstitution revealed that membrane recruitment promotes Whi3 condensation under physiological conditions. These assemblies rapidly arrest, resembling size distributions seen in cells. The temporal ordering of molecular interactions and the slow diffusion of membrane-bound complexes can limit condensate size. Our experiments reveal a trade-off between locally enhanced protein concentration at membranes, which favours condensation, and an accompanying reduction in diffusion, which restricts coarsening. Given that many condensates bind endomembranes, we predict that the biophysical properties of lipid bilayers are key for controlling condensate sizes throughout the cell.
Topics: Ribonucleoproteins
PubMed: 35411085
DOI: 10.1038/s41556-022-00882-3 -
Critical Reviews in Biochemistry and... Oct 2010Ribonucleoproteins (RNPs) play key roles in many cellular processes and often function as RNP enzymes. Similar to proteins, some of these RNPs exist and function as... (Review)
Review
Ribonucleoproteins (RNPs) play key roles in many cellular processes and often function as RNP enzymes. Similar to proteins, some of these RNPs exist and function as multimers, either homomeric or heteromeric. While in some cases the mechanistic function of multimerization is well understood, the functional consequences of multimerization of other RNPs remain enigmatic. In this review we will discuss the function and organization of small RNPs that exist as stable multimers, including RNPs catalyzing RNA chemical modifications, telomerase RNP, and RNPs involved in pre-mRNA splicing.
Topics: Animals; Humans; Models, Biological; RNA Precursors; RNA Splicing; RNA, Messenger; Ribonucleoproteins; Telomerase
PubMed: 20572804
DOI: 10.3109/10409238.2010.496772 -
Biomolecules Jun 2020The exon junction complex (EJC) is an abundant messenger ribonucleoprotein (mRNP) component that is assembled during splicing and binds to mRNAs upstream of exon-exon... (Review)
Review
The exon junction complex (EJC) is an abundant messenger ribonucleoprotein (mRNP) component that is assembled during splicing and binds to mRNAs upstream of exon-exon junctions. EJCs accompany the mRNA during its entire life in the nucleus and the cytoplasm and communicate the information about the splicing process and the position of introns. Specifically, the EJC's core components and its associated proteins regulate different steps of gene expression, including pre-mRNA splicing, mRNA export, translation, and nonsense-mediated mRNA decay (NMD). This review summarizes the most important functions and main protagonists in the life of the EJC. It also provides an overview of the latest findings on the assembly, composition and molecular activities of the EJC and presents them in the chronological order, in which they play a role in the EJC's life cycle.
Topics: Exons; Humans; RNA Splicing; RNA, Messenger; Ribonucleoproteins
PubMed: 32517083
DOI: 10.3390/biom10060866 -
Wiley Interdisciplinary Reviews. RNA Nov 2020In bacteria, mRNA decay is controlled by megadalton scale macromolecular assemblies called, "RNA degradosomes," composed of nucleases and other RNA decay associated... (Review)
Review
In bacteria, mRNA decay is controlled by megadalton scale macromolecular assemblies called, "RNA degradosomes," composed of nucleases and other RNA decay associated proteins. Recent advances in bacterial cell biology have shown that RNA degradosomes can assemble into phase-separated structures, termed bacterial ribonucleoprotein bodies (BR-bodies), with many analogous properties to eukaryotic processing bodies and stress granules. This review will highlight the functional role that BR-bodies play in the mRNA decay process through its organization into a membraneless organelle in the bacterial cytoplasm. This review will also highlight the phylogenetic distribution of BR-bodies across bacterial species, which suggests that these phase-separated structures are broadly distributed across bacteria, and in evolutionarily related mitochondria and chloroplasts. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Export and Localization > RNA Localization RNA Turnover and Surveillance > Regulation of RNA Stability.
Topics: Bacteria; Chloroplasts; Mitochondria; RNA, Messenger; Ribonucleoproteins
PubMed: 32445438
DOI: 10.1002/wrna.1599 -
Quarterly Reviews of Biophysics Feb 2011Small nucleolar and Cajal body ribonucleoprotein particles (RNPs) are required for the maturation of ribosomes and spliceosomes. They consist of small nucleolar RNA or... (Review)
Review
Small nucleolar and Cajal body ribonucleoprotein particles (RNPs) are required for the maturation of ribosomes and spliceosomes. They consist of small nucleolar RNA or Cajal body RNA combined with partner proteins and represent the most complex RNA modification enzymes. Recent advances in structure and function studies have revealed detailed information regarding ribonucleoprotein assembly and substrate binding. These enzymes form intertwined RNA-protein assemblies that facilitate reversible binding of the large ribosomal RNA or small nuclear RNA. These revelations explain the specificity among the components in enzyme assembly and substrate modification. The multiple conformations of individual components and those of complete RNPs suggest a dynamic assembly process and justify the requirement of many assembly factors in vivo.
Topics: Animals; Base Sequence; Enzymes; Humans; RNA; Ribonucleoproteins
PubMed: 21108865
DOI: 10.1017/S0033583510000235