Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing

McCool, Mason A.; Bryant, Carson J; Huang, Huey W.; Ogawa, Lisa M.; Farley-Barnes, Katherine I; Sondalle, Samuel B.; Abriola, Laura; Surovtseva, Yulia V.; Baserga, Susan J.

doi:10.1080/15476286.2023.2217392

Cited by 3 publications

(2 citation statements)

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“…We measured nucleolar 5-EU incorporation (rRNA biogenesis) in high-throughput as done previously in our laboratory [ 71 , 75 , 108 ]. In short, the nucleolar number assay was followed with the addition of a 1 mM 5-ethynl uridine (5-EU) treatment at the end of a 72-h siRNA depletion.…”

Section: Methodsmentioning

confidence: 99%

The cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis

McCool,

Bryant,

Abriola

et al. 2024

PLoS Biol

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Cancer initiates as a consequence of genomic mutations and its subsequent progression relies in part on increased production of ribosomes to maintain high levels of protein synthesis for unchecked cell growth. Recently, cytidine deaminases have been uncovered as sources of mutagenesis in cancer. In an attempt to form a connection between these 2 cancer driving processes, we interrogated the cytidine deaminase family of proteins for potential roles in human ribosome biogenesis. We identified and validated APOBEC3A and APOBEC4 as novel ribosome biogenesis factors through our laboratory’s established screening platform for the discovery of regulators of nucleolar function in MCF10A cells. Through siRNA depletion experiments, we highlight APOBEC3A’s requirement in making ribosomes and specific role within the processing and maturation steps that form the large subunit 5.8S and 28S ribosomal (r)RNAs. We demonstrate that a subset of APOBEC3A resides within the nucleolus and associates with critical ribosome biogenesis factors. Mechanistic insight was revealed by transient overexpression of both wild-type and a catalytically dead mutated APOBEC3A, which both increase cell growth and protein synthesis. Through an innovative nuclear RNA sequencing methodology, we identify only modest predicted APOBEC3A C-to-U target sites on the pre-rRNA and pre-mRNAs. Our work reveals a potential direct role for APOBEC3A in ribosome biogenesis likely independent of its editing function. More broadly, we found an additional function of APOBEC3A in cancer pathology through its function in ribosome biogenesis, expanding its relevance as a target for cancer therapeutics.

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Section: Methodsmentioning

confidence: 99%

The cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis

McCool,

Bryant,

Abriola

et al. 2024

PLoS Biol

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“…The PDFC appears to be involved in processing 3' untranslated regions (UTRs) of rRNAs [ 56 ]. Complementary efforts, based on high-throughput microscopy, are allowing for the screening of factors that coordinate the numbers and sizes of nucleolar sub-phases [ 80 ]. Overall, the rich and continually growing atlas of proteins localized to the nucleolar sub-phases represents an invaluable resource for investigating nucleolar composition.…”

Section: Nucleolar Sub-phases Are Defined By Distinct Macromolecular ...mentioning

confidence: 99%

Emergent microenvironments of nucleoli

King,

Ruff,

Pappu

2024

Nucleus

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In higher eukaryotes, the nucleolus harbors at least three sub-phases that facilitate multiple functionalities including ribosome biogenesis. The three prominent coexisting sub-phases are the fibrillar center (FC), the dense fibrillar component (DFC), and the granular component (GC). Here, we review recent efforts in profiling sub-phase compositions that shed light on the types of physicochemical properties that emerge from compositional biases and territorial organization of specific types of macromolecules. We highlight roles played by molecular grammars which refers to protein sequence features including the substrate binding domains, the sequence features of intrinsically disordered regions, and the multivalence of these distinct types of domains / regions. We introduce the concept of a barcode of emergent physicochemical properties of nucleoli. Although our knowledge of the full barcode remains incomplete, we hope that the concept prompts investigations into undiscovered emergent properties and engenders an appreciation for how and why unique microenvironments control biochemical reactions

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