Dataset Information

Profusion of G-quadruplexes on both subunits of metazoan ribosomes.

ABSTRACT: Mammalian and bird ribosomes are nearly twice the mass of prokaryotic ribosomes in part because of their extraordinarily long rRNA tentacles. Human rRNA tentacles are not fully observable in current three-dimensional structures and their conformations remain to be fully resolved. In previous work we identified sequences that favor G-quadruplexes in silico and in vitro in rRNA tentacles of the human large ribosomal subunit. We demonstrated by experiment that these sequences form G-quadruplexes in vitro. Here, using a more recent motif definition, we report additional G-quadruplex sequences on surfaces of both subunits of the human ribosome. The revised sequence definition reveals expansive arrays of potential G-quadruplex sequences on LSU tentacles. In addition, we demonstrate by a variety of experimental methods that fragments of the small subunit rRNA form G-quadruplexes in vitro. Prior to this report rRNA sequences that form G-quadruplexes were confined to the large ribosomal subunit. Our combined results indicate that the surface of the assembled human ribosome contains numerous sequences capable of forming G-quadruplexes on both ribosomal subunits. The data suggest conversion between duplexes and G-quadruplexes in response to association with proteins, ions, or other RNAs. In some systems it seems likely that the integrated population of RNA G-quadruplexes may be dominated by rRNA, which is the most abundant cellular RNA.

SUBMITTER: Mestre-Fos S

PROVIDER: S-EPMC6910669 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Profusion of G-quadruplexes on both subunits of metazoan ribosomes.

Mestre-Fos Santi S Penev Petar I PI Richards John Colin JC Dean William L WL Gray Robert D RD Chaires Jonathan B JB Williams Loren Dean LD

PloS one 20191213 12

Mammalian and bird ribosomes are nearly twice the mass of prokaryotic ribosomes in part because of their extraordinarily long rRNA tentacles. Human rRNA tentacles are not fully observable in current three-dimensional structures and their conformations remain to be fully resolved. In previous work we identified sequences that favor G-quadruplexes in silico and in vitro in rRNA tentacles of the human large ribosomal subunit. We demonstrated by experiment that these sequences form G-quadruplexes in ...[more]

PMID: 31834895

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Project description:BackgroundUpon environmental stimuli, ribosomes are surmised to undergo compositional rearrangements due to abundance changes among proteins assembled into the complex, leading to modulated structural and functional characteristics. Here, we present the ComplexOme-Structural Network Interpreter ([Formula: see text]), a computational method to allow testing whether ribosomal proteins (rProteins) that exhibit abundance changes under specific conditions are spatially confined to particular regions within the large ribosomal complex.Results[Formula: see text] translates experimentally determined structures into graphs, with nodes representing proteins and edges the spatial proximity between them. In its first implementation, [Formula: see text] considers rProteins and ignores rRNA and other objects. Spatial regions are defined using a random walk with restart methodology, followed by a procedure to obtain a minimum set of regions that cover all proteins in the complex. Structural coherence is achieved by applying weights to the edges reflecting the physical proximity between purportedly contacting proteins. The weighting probabilistically guides the random-walk path trajectory. Parameter tuning during region selection provides the option to tailor the method to specific biological questions by yielding regions of different sizes with minimum overlaps. In addition, other graph community detection algorithms may be used for the [Formula: see text] workflow, considering that they yield different sized, non-overlapping regions. All tested algorithms result in the same node kernels under equivalent regions. Based on the defined regions, available abundance change information of proteins is mapped onto the graph and subsequently tested for enrichment in any of the defined spatial regions. We applied [Formula: see text] to the cytosolic ribosome structures of Saccharomyces cerevisiae, Oryctolagus cuniculus, and Triticum aestivum using datasets with available quantitative protein abundance change information. We found that in yeast, substoichiometric rProteins depleted from translating polysomes are significantly constrained to a ribosomal region close to the tRNA entry and exit sites.Conclusions[Formula: see text] offers a computational method to partition multi-protein complexes into structural regions and a statistical approach to test for spatial enrichments of any given subsets of proteins. [Formula: see text] is applicable to any multi-protein complex given appropriate structural and abundance-change data. [Formula: see text] is publicly available as a GitHub repository https://github.com/MSeidelFed/COSNet_i and can be installed using the python installer pip.

Dataset Information

Profusion of G-quadruplexes on both subunits of metazoan ribosomes.

Publications

Profusion of G-quadruplexes on both subunits of metazoan ribosomes.

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