Crystal structure of a dimerization domain of human Caprin-1: insights into the assembly of an evolutionarily conserved ribonucleoprotein complex consisting of Caprin-1, FMRP and G3BP1

Wu, Yuhong; Zhu, Jiang; Huang, Xiaolan; Du, Zhihua

doi:10.1107/s2059798316004903

Cited by 25 publications

(46 citation statements)

References 47 publications

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“…5D). One of the reasons for this may be direct binding of the scaffolds (27). Taken together, these results supported the observation that S-and R-scaffolds formed distinct substructures in granules and suggested that the scaffolds were not randomly mixed but localized in a moderate order in the granules.…”

Section: Liquid-and Solid-like Rna Granule Formation and Combinationsupporting

confidence: 85%

“…This interaction may be mediated by direct binding between specific R-and S-scaffolds, e.g. FMR1 and RNG105 (27). However, such relatively strong binding will inhibit separation of R-and S-substructures if the scaffolds were abundantly expressed, as observed in the cells expressing FMR1 and RNG105 (Fig.…”

Section: Liquid-and Solid-like Rna Granule Formation and Combinationmentioning

confidence: 99%

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Liquid- and solid-like RNA granules form through specific scaffold proteins and combine into biphasic granules

Shiina

2019

Journal of Biological Chemistry

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Edited by Karin Musier-Forsyth RNA granules consist of membrane-less RNA-protein assemblies and contain dynamic liquid-like shells and stable solid-like cores, which are thought to function in numerous processes in mRNA sorting and translational regulation. However, how these distinct substructures are formed, whether they are assembled by different scaffolds, and whether different RNA granule scaffolds induce these different substructures remains unknown. Here, using fluorescence microscopy-based morphological and molecular-dynamics analyses, we demonstrate that RNA granule scaffold proteins (scaffolds) can be largely classified into two groups, liquid and solid types, which induce the formation of liquid-like and solid-like granules, respectively, when expressed separately in cultured cells. We found that when co-expressed, the liquid-type and solid-type scaffolds combine and form liquid-and solid-like substructures in the same granules, respectively. The combination of the different types of scaffolds reduced the immobile fractions of the solid-type scaffolds and their dose-dependent ability to decrease nascent polypeptides in granules, but had little effect on the dynamics of the liquidtype scaffolds or their dose-dependent ability to increase nascent polypeptides in granules. These results suggest that solidand liquid-type scaffolds form different substructures in RNA granules and differentially affect each other. Our findings provide detailed insight into the assembly mechanism and distinct dynamics and functions of core and shell substructures in RNA granules.

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Section: Liquid-and Solid-like Rna Granule Formation and Combinationsupporting

confidence: 85%

Section: Liquid-and Solid-like Rna Granule Formation and Combinationmentioning

confidence: 99%

Liquid- and solid-like RNA granules form through specific scaffold proteins and combine into biphasic granules

Shiina

2019

Journal of Biological Chemistry

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“…The data presented in this study indicate that miR-193a targets the 3′UTR of Caprin-1 mRNA, leading to inhibition of production of caprin-1 protein. Caprin-1 is known to regulate the cell cycle and cell proliferation 46 47 48 . Caprin-1 directly binds to mRNAs for G3BP1 protein 46 48 , c-MYC (ref.…”

Section: Discussionmentioning

confidence: 99%

“…Caprin-1 is known to regulate the cell cycle and cell proliferation 46 47 48 . Caprin-1 directly binds to mRNAs for G3BP1 protein 46 48 , c-MYC (ref. 47 ) and cyclin D2 through its carboxy-terminal RGG-rich region.…”

Section: Discussionmentioning

confidence: 99%

MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression

et al. 2017

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Exosomes are emerging mediators of intercellular communication; whether the release of exosomes has an effect on the exosome donor cells in addition to the recipient cells has not been investigated to any extent. Here, we examine different exosomal miRNA expression profiles in primary mouse colon tumour, liver metastasis of colon cancer and naive colon tissues. In more advanced disease, higher levels of tumour suppressor miRNAs are encapsulated in the exosomes. miR-193a interacts with major vault protein (MVP). Knockout of MVP leads to miR-193a accumulation in the exosomal donor cells instead of exosomes, inhibiting tumour progression. Furthermore, miR-193a causes cell cycle G1 arrest and cell proliferation repression through targeting of Caprin1, which upregulates Ccnd2 and c-Myc. Human colon cancer patients with more advanced disease show higher levels of circulating exosomal miR-193a. In summary, our data demonstrate that MVP-mediated selective sorting of tumour suppressor miRNA into exosomes promotes tumour progression.

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“…The overall protein fold and dimeric structure assumed by the dCaprin fragments are similar to those of Caprin-1 and Caprin-2 we determined previously (Figure 2A and B). 18 The most noticeable difference between the dCaprin and Caprin-1 or Caprin-2 structures is that the α1 helix in the dCaprin structure is shorter (by about one and a half helical turns) than the one in the Caprin-1 or Caprin-2 structure (Figure 2A and B…”

Section: Data Collection Data Processing and Structure Determinationmentioning

confidence: 99%

Crystal structure of a 123 amino acids dimerization domain of Drosophila Caprin

et al. 2020

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Cytoplasmic activation/proliferation-associated protein (Caprin) proteins assume diverse functions in many important biological processes, including synaptic plasticity, stress response, innate immune response, and cellular proliferation. The Caprin family members are characterized by the presence of a highly conserved homologous region (HR1) at the N-terminus and arginine-glycine-rich (RGG) boxes at the C-terminus. We had previously determined the crystal structures of human Caprin-1 and Caprin-2 fragments corresponding to the C-terminal 2/3 of HR1. Both fragments adopt homodimeric structures. Based on sequence conservation, we speculated that all Caprin proteins should have similar homodimeric structures. Here we report the crystal structure of a fragment (residues 187-309) of Drosophila melanogaster Caprin (dCaprin). The dCaprin fragment adopts an all α-helical fold which self-associates to form a homodimer. The overall dCaprin homodimeric structure is similar to the Caprin-1 and Caprin-2 homodimeric structures. Most of the amino acids residues mediating homodimerization in the three structures are conserved among all Caprin family members. These structural and sequence data suggest that homodimerization through a conserved dimerization domain is a common structural feature of the Caprin protein family. The dimeric structures may also be involved in interaction with Caprin partners. Dimer formation creates a V-shape concave surface that may serve as a protein binding groove. The concave surfaces in Caprin-1, Caprin-2, and dCaprin should have different and specific binding partners due to the large difference in electrostatic potentials. We propose the existence of a multi-functional domain in Caprin proteins, which not only mediate homodimerization but also involve in interaction with specific Caprin partners.

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Crystal structure of a dimerization domain of human Caprin-1: insights into the assembly of an evolutionarily conserved ribonucleoprotein complex consisting of Caprin-1, FMRP and G3BP1

Cited by 25 publications

References 47 publications

Liquid- and solid-like RNA granules form through specific scaffold proteins and combine into biphasic granules

Liquid- and solid-like RNA granules form through specific scaffold proteins and combine into biphasic granules

MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression

Crystal structure of a 123 amino acids dimerization domain of Drosophila Caprin

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