Eukaryotic small ribosomal subunits are first assembled into 90S pre-ribosomes. The complete 90S is a gigantic complex with a molecular mass of approximately five megadaltons. Here, we report the nearly complete architecture of Saccharomyces cerevisiae 90S determined from three cryo-electron microscopy single particle reconstructions at 4.5 to 8.7 angstrom resolution. The majority of the density maps were modeled and assigned to specific RNA and protein components. The nascent ribosome is assembled into isolated native-like substructures that are stabilized by abundant assembly factors. The 5' external transcribed spacer and U3 snoRNA nucleate a large subcomplex that scaffolds the nascent ribosome. U3 binds four sites of pre-rRNA, including a novel site on helix 27 but not the 3' side of the central pseudoknot, and crucially organizes the 90S structure. The 90S model provides significant insight into the principle of small subunit assembly and the function of assembly factors.DOI:
http://dx.doi.org/10.7554/eLife.22086.001
With recent progress in photothermal materials, organic small molecules featured with flexibility, diverse structures, and tunable properties exhibit unique advantages but have been rarely applied in solar‐driven water evaporation owing to limited sunlight absorption resulting in low solar–thermal conversion. Herein, a stable croconium derivative, named CR‐TPE‐T, is designed to exhibit the unique biradical property and strong π–π stacking in the solid state, which facilitate not only a broad absorption spectrum from 300 to 1600 nm for effective sunlight harvesting, but also highly efficient photothermal conversion by boosting nonradiative decay. The photothermal efficiency is evaluated to be 72.7% under 808 nm laser irradiation. Based on this, an interfacial‐heating evaporation system based on CR‐TPE‐T is established successfully, using which a high solar‐energy‐to‐vapor efficiency of 87.2% and water evaporation rate of 1.272 kg m−2 h−1 under 1 sun irradiation are obtained, thus making an important step toward the application of organic‐small‐molecule photothermal materials in solar energy utilization.
The 90S preribosome is a large, early assembly intermediate of small ribosomal subunits that undergoes structural changes to give a pre-40S ribosome. Here, we gained insight into this transition by determining cryo–electron microscopy structures of Saccharomyces cerevisiae intermediates in the path from the 90S to the pre-40S. The full transition is blocked by deletion of RNA helicase Dhr1. A series of structural snapshots revealed that the excised 5′ external transcribed spacer (5′ ETS) is degraded within 90S, driving stepwise disassembly of assembly factors and ribosome maturation. The nuclear exosome, an RNA degradation machine, docks on the 90S through helicase Mtr4 and is primed to digest the 3′ end of the 5′ ETS. The structures resolved between 3.2- and 8.6-angstrom resolution reveal key intermediates and the critical role of 5′ ETS degradation in 90S progression.
The hypoxia of the tumor microenvironment (TME) seriously restricts the photodynamic therapy (PDT) effect of conventional type-II photosensitizers, which are highly dependent on O 2 . In this work, a new type-I photosensitizer (TPE-TeV-PPh 3 ) consisting of a tetraphenylethylene group (TPE) as a bioimaging moiety, triphenyl-phosphine (PPh 3 ) as a mitochondria-targeting group, and telluroviologen (TeV 2+ ) as a reactive oxygen species (O 2•− , •OH) generating moiety is developed. The luminescence intensity of TPE-TeV-PPh 3 increased significantly after specific oxidation by excess H 2 O 2 in the TME without responding to normal tissues via the formation of Te═O bond, which can be used for monitoring abnormal H 2 O 2 , positioning, and imaging of tumors. TPE-TeV-PPh 3 with highly reactive radicals generation and stronger hypoxia tolerance realizes efficient cancer cell killing under hypoxic conditions, achieving 88% tumor growth inhibition. Therefore, TPE-TeV-PPh 3 with low phototoxicity in normal tissue achieves tumor imaging and effective PDT toward solid tumors in response to high concentrations of H 2 O 2 in the TME, which provides a new strategy for the development of type-I photosensitizers.
K E Y W O R D S photodynamic anti-cancer therapy, telluroviologen, tumor imaging, type-I photosensitizer
INTRODUCTIONCancer is a major threat to human health and development. [1] Traditional cancer therapies, including surgery, chemotherapy, and radiotherapy, have been used clinically for decades, but they have inherent shortcomings. For example, surgery requires chemotherapy and radiotherapy for adjuvant treatment after tumor removal to prevent recurrence and deterioration. [2] However, radiotherapy and chemotherapy are always accompanied by serious side effects and resistance during treatment. [3] Compared with traditional therapy methods, photodynamic therapy (PDT) has received increasing attention due to its low systemic toxicity, high selectivity, and reduced trauma without drug/radiation resistance. [4] The main mechanism of action is to employ a light source to excite the photosensitizer to produce reactive oxygen Qi Sun and Qi Su contributed equally to this work.
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