![]() RNA-binding modules are versatile elements ( figure 1). RNA-binding modules are versatile elements with variable affinity and specificity for RNAīefore we discuss how RNA-binding modules combine with one another, we first briefly review the principles underlying their characteristics. The assembled state can result in new RNA-binding specificity and/or affinity that further the function of RBPs within the cell.Ģ. As in individual proteins where IDRs link RNA-binding modules, in higher-order assemblies, IDRs can connect proteins and RNA resulting in complexes that have the characteristics of multi-modular entities. We propose an analogy between intra-protein linkers and assembly-promoting IDRs. IDRs can also function to connect structural elements between and among proteins and RNA promoting the formation of higher-order RNA–protein assemblies. The structural constraints and topologies defined by linkers define the RNA targets of a single RBP. IDRs often behave as linkers connecting RNA-binding modules within a single RBP where they dictate how modules are arranged and relate to each other. We illustrate the crucial role of IDRs in defining RNA-binding affinity and sequence specificity. In this review, we discuss the modular characteristics of RBPs and how modularity is exploited to mediate interactions with the target RNA. Structures were visualized with PyMOL, version 2.4. The zinc atom in ( c) is depicted as a yellow sphere. ![]() Protein α-helices are depicted in orange (with the exception of the QUA2 region, which is depicted in green), β-sheets in teal and loops in black. In all panels, RNA is represented in magenta. ( c) Zinc finger of FUS interacting with UGGUG RNA (PDB ID 6g99). ( b) KH domain and QUA2 region of splicing factor 1 (SF1) complexed with UAUACUAACAA RNA (PDB ID 1k1g). ( a) RRM1 of the polypyrimidine tract-binding protein (PTB) interacting with CUCUCU RNA (PDB ID 2ad9). Selected examples of RNA-binding modules. The highly varied functions of these assemblies reflect a diverse composition, raising the question of how selected proteins and RNAs are recruited to the correct assembly.įigure 1. These flexible regions facilitate the formation of large non-stoichiometric assemblies, such as membrane-less compartments and amyloid-like structures. Furthermore, RBPs typically contain extended intrinsically disordered regions (IDRs) that have the ability to mediate protein–protein and RNA–protein interactions. To achieve proper affinity and specificity, most RBPs combine several RNA-binding modules through disordered linkers. Nevertheless, many RBPs have specific targets and can bind them tightly, raising the question of how these proteins reach the binding abilities necessary for their function. ![]() Individual RNA-binding modules typically bind between two and six nucleotides, underscoring their generally low binding affinity and sequence specificity. RBPs contact RNA through structural elements called RNA-binding modules ( figure 1). In this review, we refer to discrete structural elements that are able to carry out an independent function as modules. RNA-binding proteins (RBPs) have a typical modular structure, where RNA-binding, catalytic and regulatory elements are combined together to define the targets and the function of these proteins. RNA–protein complexes are termed ribonucleoprotein (RNPs) particles. ![]() ![]() The assembled state generates additional RNA-binding specificity and affinity properties that contribute to further the function of RNA-binding proteins within the cellular environment.Īll steps of metabolism and function of a large fraction of RNAs, including messenger (m) RNAs, ribosomal (r) RNAs and several non-coding RNAs, require interaction with proteins. We discuss how these regions can connect proteins and RNA resulting in heterogeneous higher-order assemblies such as membrane-less compartments and amyloid-like structures that have the characteristics of multi-modular entities. RNA-binding proteins also often contain extended intrinsically disordered regions that mediate protein–protein and RNA–protein interactions with multiple partners. Here, we review how disordered linkers connecting RNA-binding modules govern the specificity and affinity of RNA–protein interactions by regulating the effective concentration of these modules and their relative orientation. RNA-binding proteins typically attain the physiological specificity and affinity for their RNA targets by combining several RNA-binding modules. Most RNA-binding modules are small and bind few nucleotides. ![]()
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