Native RNP/Sm Antigen

Ribonucleoprotein (RNP) bodies or particles are membrane-free structures that can be seen under a light microscope and are assembled by the interaction of intracellular RNA and proteins. Some RNP bodies appear constitutively in cells, such as cytoplasmic processing bodies (P-bodies), TIS bodies, U bodies, Cajal bodies, nucleoli, nuclear speckles, paraspeckles, etc. Some RNP particles are formed when translation is inhibited or ribosomes escape, such as stress granules and P bodies. Some RNP particles come from double-stranded RNA and play a role in immune response. Some RNP particles only appear in certain cell types. The widespread existence of RNP particles shows that there are many similarities and differences in the formation and functions of these particles. The assembly of RNP particles is mainly formed by the aggregation of proteins and RNA through biomolecules, and depends on the multivalent interactions between proteins-proteins, proteins-RNAs, and RNA-RNAs inside the particles. These proteins and RNAs eventually form various functional particles or bodies through liquid-liquid phase separation or liquid-solid phase separation. From the compositional analysis, in the particles formed by some small functional RNAs, the composition ratio of RNA and protein is about 20% and 80% respectively, such as U1 snRNP. In this RNP particle, due to the relatively small amount of exposed snRNA, there are relatively few intermolecular RNA-RNA interactions. In contrast, the particles formed by mRNA contain a large number of RNA bases, RNA-RNA interactions are relatively rich, and the mass ratio of protein to mRNA in this particle can reach 1:1. In addition, studies have shown that the number of RBPs in the nucleus far exceeds that in the cytoplasm, indicating that most mRNAs in the cytoplasm are bound to ribosomes, and most untranslated mRNAs in the cytoplasm do not bind to RBPs. In the formation of RNP particles or bodies, the interaction between proteins is very critical. Whether it is stress granules or P bodies, the interaction between some key proteins is necessary for the formation of particles or bodies. In contrast, the intrinsically disordered regions (IDRs) in some RBPs are not important for the formation of particles, while the interaction between well-folded domains plays a key role in the formation of particles or bodies. RNA is a key molecule in the formation of RNP particles. First, RNA can act as a linker molecule and can recruit numerous RBPs proteins to bind. Second, the interaction between RNA-RNA is crucial for the formation of RNP particles. Third, RNA tends to promote the formation of RNPs through self-assembly.

Figure 1. Models for RNP (ribonucleoprotein) assembly and function. (Sources: Ye Q, et al. 2012)

The condensation of biological molecules is a concentration-dependent assembly mode of macromolecules, but RNP particles do not strictly follow the principle of thermodynamic equilibrium, but are affected by the energy-dependent addition and removal rates of components. Therefore, the composition of particles is regulated by assembly dynamics. The formation of RNP particles depends on the compression of dispersed components in the cytoplasm or nucleus. This compression occurs through the interaction between proteins and RNA. When the concentration of the complex reaches saturation concentration, RNP particles are finally formed. When RNPs are produced or located in certain special locations, component compression will also occur, resulting in an increase in component concentration. Only when RNP particles reach saturation concentration will RNP particles begin to assemble and form. In addition, when the component concentration has not yet reached saturation concentration, these components may first compress to form some small RNP clusters, and then these small clusters will combine with each other to form larger RNP particles or bodies, which reflects a stage-by-stage gradual state of the formation of RNP particles or bodies. After RNP particles begin to form, highly concentrated RNA and proteins promote the interaction between molecules, which in turn promotes the stability of RNP particles. The interactions between RNPs can be divided into homotypic and heterotypic interactions depending on whether the two RNP types are the same. Many RNP particles can contact and fuse, including homotypic and heterotypic RNP particles. After the contact and fusion of homotypic RNPs, there will be a redistribution of molecular interactions, and eventually new molecular interactions and new RNP particles will be formed. Heterotypic RNPs do not fuse after contact, such as stress granules and P bodies. Different RNP particles will form heterotypic interactions on the surfaces they contact. The contact of heterotypic RNPs will promote the movement of RNPs between stress granules and P bodies, but this situation is rare.

The assembly of RNP particles is regulated in many ways, including post-translational modifications of RNP particle proteins, protein chaperones, RBPs, and DEAD-box RNA helicases. The types of post-translational modifications that affect the assembly of RNP particles include methylation, phosphorylation, acetylation, N-glycosylation, PARylation, and ubiquitination. These modifications mainly affect the assembly of RNP particles by changing protein-protein and protein-RNA interactions. Molecular chaperones and adaptor proteins can regulate the formation and disassembly of RNPs. In addition, there is a protein network in RNP particles that can regulate RNA-RNA interactions, which is called the RNA chaperone network. RBP proteins eIF4A and YB-1 are both key components. DEAD-box proteins can both positively and negatively regulate the formation of RNP particles. DEAD-box proteins exert their regulatory effects by replacing proteins that promote or inhibit the formation of RNP particles from RNAs. RNP particle formation has multiple biological functions, and the functions of RNP can be inferred from the following two aspects: First, if the key protein of a certain signaling pathway is concentrated and participates in RNP particle formation, then this signaling pathway will be affected. For example, P bodies regulate RNA degradation by concentrating RNA degradation-related proteins. Other cytoplasmic RNP particles, such as stress granules, sperm and neural mRNP particles, are mainly composed of untranslated mRNPs, and their functions involve translation inhibition. Second, if knocking out a certain protein causes changes in RNP particle formation and changes in cell function, then this RNP particle is related to this cell function.

RNP Complex
RNA-Protein Complex
Ribonucleic Acid-Protein Complex
RNA-Binding Protein
Ribonucleic Protein
RNA-Protein Particle
Nucleoprotein-RNA Complex
RNA-Associated Protein