Cryo-EM structure of a late pre-40S ribosomal subunit from Saccharomyces cerevisiae

Heuer, André; Thomson, Emma; Schmidt, Christian M.; Berninghausen, Otto; Becker, Thomas; Hurt, Ed; Beckmann, Roland

doi:10.7554/elife.30189

Cited by 80 publications

(160 citation statements)

References 46 publications

(75 reference statements)

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“…In the monomeric form of ctRio2, the C-terminal helix is incompatible with dimer formation and participates in interactions around the catalytic centre which might include an auto-inhibitory action toward ATP catalysis 26 . Finally, in the pre-40S particle cryo-EM reconstruction, this eukaryotic specific a-helix is not observed 28,29 .…”

Section: Discussionmentioning

confidence: 83%

“…In the LegK4 structure, the protein dimerizes through aF, aG and the aG-aI loop of the Clobe in both the apo and AMP-PNP bound states, which differs from the dimer formation observed for hRIO2. Finally, In the cryo-EM reconstructions of yeast and human pre-40S particles, only a protomer of Rio2 protein could be fit into the attributed density for Rio2 26,28,29,40,41 . Altogether, these data strongly suggest that the in vitro dimeric form of RIO2 is an inactive form.…”

Section: Discussionmentioning

confidence: 99%

“…4C to 4E). Of note, the same surface area is used for the association of Rio2 with 20S pre-rRNA (helices 1, 18, 28, 34, and 44), Tsr1, Ltv1, uS12, us7, uS13 and uS19 28,29 . The overlapping mechanism for a subset of residues that are involved in pre-40S particle association and dimer formation suggests that if dimerization exist in vivo, it is incompatible with pre-40S association.…”

Section: Rio2 Homodimerization Surface Is Conserved In Eukaryotesmentioning

confidence: 99%

“…This observation is in agreement with the absence of the ctRio2 dimer in AUC experiments. It is also interesting to note that the eukaryotic-specific aI helix is disordered in the recent structure of the pre-40S particle 28,29 , suggesting that the aI is a mobile secondary structure that may not be involved in ATP catalysis in pre-40S maturation.…”

Section: Rio2 Homodimerization Surface Is Conserved In Eukaryotesmentioning

confidence: 99%

“…Altogether, these observations led to the proposal that Rio2 is rather an ATPase than a protein kinase. Finally, the position of Rio2 on the pre-40S particle has been established at the P-site close to domain IV of Tsr1, where both proteins block the A-and P-sites on the 40S subunit 28,29 .…”

Section: Introductionmentioning

confidence: 99%

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Dimerization of human Rio2 kinase/ATPase locks its ATP-binding site in an apo state

Maurice

Pérébaskine

Fribourg³

2019

Preprint

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Rio proteins form a conserved family of atypical protein kinases. Rio2 is a serine/threonine protein kinase/ATPase involved in pre-40S ribosomal maturation. Current crystal structures of archaeal and fungi Rio2 proteins report a monomeric form of the protein. Here, we describe three atomic structures of the human Rio2 kinase showing that it forms a homodimer. Upon self-association, the ATP-binding pocket is hidden from the solvent and the protein is locked in an apo state corresponding to an inactive form of the kinase. The homodimerization is mediated by key residues previously shown to be responsible for ATP binding and catalysis. This unusual protein kinase dimer reveals an intricate mechanism of mutually exclusive substrate binding and oligomeric state formation. We propose that this oligomeric state could serve a dual function in maintaining the protein in an inactive state and being a novel type of nuclear import signal.Significance StatementRio kinases form a family of atypical protein kinases that are believed to be ATPases rather than kinases. The three members of the Rio family are involved in ribosome biogenesis. We show here that contrarily to what was reported so far, Rio2 is able homodimerize in a conformation that locks it in an apo state, preventing its (re)association to pre-mature ribosomes. This unconventional self-association is not seen in any other protein kinase. This mechanism is likely to be transient and could used to efficiently re-import the protein to the nucleus.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Rio2 Homodimerization Surface Is Conserved In Eukaryotesmentioning

confidence: 99%

Section: Rio2 Homodimerization Surface Is Conserved In Eukaryotesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dimerization of human Rio2 kinase/ATPase locks its ATP-binding site in an apo state

Maurice

Pérébaskine

Fribourg³

2019

Preprint

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Ribosomal protein uS3 in cell biology and human disease: Latest insights and prospects

Graifer

Карпова

2020

BioEssays

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The conserved ribosomal protein uS3 in eukaryotes has long been known as one of the essential components of the small (40S) ribosomal subunit, which is involved in the structure of the 40S mRNA entry pore, ensuring the functioning of the 40S subunit during translation initiation. Besides, uS3, being outside the ribosome, is engaged in various cellular processes related to DNA repair, NF-kB signaling pathway and regulation of apoptosis. This review is devoted to recent data opening new horizons in understanding the roles of uS3 in such processes as the assembly and maturation of 40S subunits, ensuring proper structure of 48S pre-initiation complexes, regulation of initiation and ribosome-based RNA quality control pathways. Besides, we summarize novel results on the participation of the protein in processes beyond translation and consider biomedical implications of previously known and recently found extra-ribosomal functions of uS3, primarily, in oncogenesis.

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snoRNAs in hematopoiesis and blood malignancies: A comprehensive review

Challakkara,

Chhabra

2023

Journal Cellular Physiology

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Small nucleolar RNAs (snoRNAs) are noncoding RNA molecules of highly variable size, usually ranging from 60 to 150 nucleotides. They are classified into H/ACA box snoRNAs, C/D box snoRNAs, and scaRNAs. Their functional profile includes biogenesis of ribosomes, processing of rRNAs, 2′‐O‐methylation and pseudouridylation of RNAs, alternative splicing and processing of mRNAs and the generation of small RNA molecules like miRNA. The snoRNAs have been observed to have an important role in hematopoiesis and malignant hematopoietic conditions including leukemia, lymphoma, and multiple myeloma. Blood malignancies arise in immune system cells or the bone marrow due to chromosome abnormalities. It has been estimated that annually over 1.25 million cases of blood cancer occur worldwide. The snoRNAs often show a differential expression profile in blood malignancies. Recent reports associate the abnormal expression of snoRNAs with the inhibition of apoptosis, uncontrolled cell proliferation, angiogenesis, and metastasis. This implies that targeting snoRNAs could be a potential way to treat hematologic malignancies. In this review, we describe the various functions of snoRNAs, their role in hematopoiesis, and the consequences of their dysregulation in blood malignancies. We also evaluate the potential of the dysregulated snoRNAs as biomarkers and therapeutic targets for blood malignancies.

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Cryo-EM structure of a late pre-40S ribosomal subunit from Saccharomyces cerevisiae

Cited by 80 publications

References 46 publications

Dimerization of human Rio2 kinase/ATPase locks its ATP-binding site in an apo state

Dimerization of human Rio2 kinase/ATPase locks its ATP-binding site in an apo state

Ribosomal protein uS3 in cell biology and human disease: Latest insights and prospects

snoRNAs in hematopoiesis and blood malignancies: A comprehensive review

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