The ribosome assembly factor Nop53 has a structural role in the formation of nuclear pre-60S intermediates, affecting late maturation events

Bagatelli, Felipe F.M.; Vitorino, Francisca Nathália de Luna; Cunha, Júlia Pinheiro Chagas da; Oliveira, Carla C.

doi:10.1093/nar/gkab494

Cited by 8 publications

(7 citation statements)

References 108 publications

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“…3A), the GDP-bound GTPB4 GTPase domain first appears in state B and remains GDPbound in all subsequent nucleolar and nuclear states that we observe (Figs. [42][43][44] appear, these data indicate that the incorporation of these RNA elements is coupled to the GTPase activity of GTPB4. The incorporation of GTPB4 after GTP hydrolysis is therefore similar to other enzymes with ATPase or methyltransferase activity (10,35).…”

Section: Gtpb4 Catalyzes the Initial Installation Of The Peptidyl Tra...mentioning

confidence: 67%

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Principles of human pre-60Sbiogenesis

Broeck

Klinge

2023

Preprint

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During early stages of human large ribosomal subunit (60S) biogenesis, an ensemble of assembly factors establishes and fine-tunes the essential RNA functional centers of pre-60Sparticles by an unknown mechanism. Here, we report a series of cryo-electron microscopy structures of human nucleolar and nuclear pre-60Sassembly intermediates at resolutions of 2.5-3.2 angstroms. These structures show how protein interaction hubs tether assembly factor complexes to nucleolar particles and how GTPases and ATPases couple irreversible nucleotide hydrolysis steps to the installation of functional centers. Nuclear stages highlight how a conserved RNA processing complex, the rixosome, couples large-scale RNA conformational changes to pre-rRNA processing by the RNA degradation machinery. Our ensemble of human pre-60Sparticles provides a rich foundation to elucidate the molecular principles of ribosome formation.

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Section: Gtpb4 Catalyzes the Initial Installation Of The Peptidyl Tra...mentioning

confidence: 67%

“…S27 ). The involvement of the NOP53 sensor domain is supported by biochemical data showing that N-terminal truncations of this domain result in ITS2 processing defects ( 44 ).…”

Section: Main Textmentioning

confidence: 93%

Principles of human pre-60Sbiogenesis

Broeck

Klinge

2023

Preprint

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“…S28). The involvement of the NOP53 sensor domain is supported by biochemical data showing that N-terminal truncations of this domain result in ITS2-processing defects ( 44 ).…”

Section: The Rixosome and Nop53 Couple 5s Rnp Rotation To Its2 Proces...mentioning

confidence: 92%

Principles of human pre-60 S biogenesis

Broeck

Klinge

2023

Science

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During the early stages of human large ribosomal subunit (60 S ) biogenesis, an ensemble of assembly factors establishes and fine-tunes the essential RNA functional centers of pre-60 S particles by an unknown mechanism. Here, we report a series of cryo–electron microscopy structures of human nucleolar and nuclear pre-60 S assembly intermediates at resolutions of 2.5 to 3.2 angstroms. These structures show how protein interaction hubs tether assembly factor complexes to nucleolar particles and how guanosine triphosphatases and adenosine triphosphatase couple irreversible nucleotide hydrolysis steps to the installation of functional centers. Nuclear stages highlight how a conserved RNA-processing complex, the rixosome, couples large-scale RNA conformational changes with pre–ribosomal RNA processing by the RNA degradation machinery. Our ensemble of human pre-60 S particles provides a rich foundation with which to elucidate the molecular principles of ribosome formation.

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“…NOP53 (also known as GLTSCR2 or PICT1) is one of the nucleolar proteins with crucial functions in cell growth and homeostasis, including ribosome biogenesis and DNA damage response [ 21 , 22 ]. NOP53 knockdown decreased both the presence of γ-H2AX at the nuclear and the activation of multiple DDR factors, which further sensitized cells to DNA damage [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

NOP53 undergoes liquid-liquid phase separation and promotes tumor radio-resistance

et al. 2022

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Aberrant DNA damage response (DDR) axis remains the major molecular mechanism for tumor radio-resistance. We recently characterized liquid-liquid phase separation (LLPS) as an essential mechanism of DDR, and identified several key DDR factors as potential LLPS proteins, including nucleolar protein NOP53. In this study, we found that NOP53 formed highly concentrated droplets in vivo and in vitro, which had liquid-like properties including the fusion of adjacent condensates, rapid fluorescence recovery after photobleaching and the sensitivity to 1,6-hexanediol. Moreover, the intrinsically disordered region 1 (IDR1) is required for NOP53 phase separation. In addition, multivalent-arginine-rich linear motifs (M-R motifs), which are enriched in NOP53, were essential for its nucleolar localization, but were dispensable for the LLPS of NOP53. Functionally, NOP53 silencing diminished tumor cell growth, and significantly sensitized colorectal cancer (CRC) cells to radiotherapy. Mechanically, NOP53 negatively regulated p53 pathway in CRC cells treated with or without radiation. Importantly, data from clinical samples confirmed a correlation between NOP53 expression and tumor radio-resistance. Together, these results indicate an important role of NOP53 in radio-resistance, and provide a potential target for tumor radio-sensitization.

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The ribosome assembly factor Nop53 has a structural role in the formation of nuclear pre-60S intermediates, affecting late maturation events

Cited by 8 publications

References 108 publications

Principles of human pre-60Sbiogenesis

Principles of human pre-60Sbiogenesis

Principles of human pre-60 S biogenesis

NOP53 undergoes liquid-liquid phase separation and promotes tumor radio-resistance

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