Identification of distinct maturation steps involved in human 40S ribosomal subunit biosynthesis

Nieto, Blanca; Gaspar, Sonia G.; Moriggi, Giulia; Pestov, Dimitri G.; Bustelo, Xosé R.; Dosil, Mercedes

doi:10.1038/s41467-019-13990-w

Cited by 22 publications

(32 citation statements)

References 52 publications

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“…To delineate the molecular mechanism at the origin of this phenotype, we analyzed pre-rRNA processing in RIOK2 WT Pre-40S particles containing the 18S-E pre-rRNA are generated in the nucleolus [64]. They undergo maturation steps in the nucleoplasm before being exported to the cytoplasm, where final maturation events lead to the production of the mature 18S rRNA of the 40S subunit [4].…”

Section: Riok2 Phosphorylation At Ser483 Is Required For Efficient Maturation Of Pre-40s Particlesmentioning

confidence: 99%

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RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit

et al. 2021

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Ribosome biogenesis lies at the nexus of various signaling pathways coordinating protein synthesis with cell growth and proliferation. This process is regulated by well-described transcriptional mechanisms, but a growing body of evidence indicates that other levels of regulation exist. Here we show that the Ras/mitogen-activated protein kinase (MAPK) pathway stimulates post-transcriptional stages of human ribosome synthesis. We identify RIOK2, a pre-40S particle assembly factor, as a new target of the MAPK-activated kinase RSK. RIOK2 phosphorylation by RSK stimulates cytoplasmic maturation of late pre-40S particles, which is required for optimal protein synthesis and cell proliferation. RIOK2 phosphorylation facilitates its release from pre-40S particles and its nuclear re-import, prior to completion of small ribosomal subunits. Our results bring a detailed mechanistic link between the Ras/MAPK pathway and the maturation of human pre-40S particles, which open a hitherto poorly explored area of ribosome biogenesis.

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Section: Riok2 Phosphorylation At Ser483 Is Required For Efficient Maturation Of Pre-40s Particlesmentioning

confidence: 99%

“… (A) Schematic representation of pre-rRNA processing in human cells, adapted from [ 1 ] with precursor subcellular localization from [ 64 ]. Position of the probes (ITS1 and ITS2) used in Northern blot (NB) experiments to detect the pre-rRNAs are indicated.…”

Section: Supporting Informationmentioning

confidence: 99%

RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit

et al. 2021

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“…Very recently, we observed that the cytoplasmic PARN can locate on the endoplasmic reticulum (ER) via its CTD and shuttle between the cytosol and ER surface (Duan et al, 2020). Consistent with its multiple cellular locations, PARN not only regulates mRNA decay in the nucleus and cytoplasm, but also plays a crucial role in the biogenesis of various noncoding RNAs (ncRNAs) including microRNA (miRNAs) (Shukla, Bjerke, Muhlrad, Yi, & Parker, 2019), small nuclear RNAs (Berndt et al, 2012; Duan et al, 2019), telomere RNAs (Dhanraj et al, 2015; Moon et al, 2015), ribosomal RNAs (Benyelles et al, 2019; Ishikawa et al, 2017; Montellese et al, 2017; Nieto et al, 2020), and Y RNA (Shukla & Parker, 2017).…”

Section: Parn In Ddr and Genomic Stabilitymentioning

confidence: 99%

“…Besides miRNA, PARN also acts as a 3′‐end trimmer of snoRNAs (Berndt et al, 2012; Dhanraj et al, 2015; Duan et al, 2019; Son, Park, & Kim, 2018), telomere RNA (Benyelles et al, 2019; Boyraz et al, 2016; Deng et al, 2019; Dhanraj et al, 2015; Dodson et al, 2019; Mason & Bessler, 2015; Moon et al, 2015; Nguyen et al, 2015; Roake et al, 2019; Shukla, Schmidt, Goldfarb, Cech, & Parker, 2016; Stuart et al, 2015; Tummala et al, 2015), rRNA (Benyelles et al, 2019; Ishikawa et al, 2017; Montellese et al, 2017; Nieto et al, 2020), and Y RNA (Shukla & Parker, 2017). It is worth noting that a PARN homologue, PARN‐like domain‐containing 1 (PNLDC1) contributes to piRNA biogenesis in silkworms, Caenorhabditis elegans , and mammalians (Ding et al, 2017; Izumi et al, 2016; Tang, Tu, Lee, Weng, & Mello, 2016).…”

Section: Parn In Ddr and Genomic Stabilitymentioning

confidence: 99%

Diverse functions of deadenylases in DNA damage response and genomic integrity

Yan

2020

WIREs RNA

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DNA damage response (DDR) is a coordinated network of diverse cellular processes including the detection, signaling, and repair of DNA lesions, the adjustment of metabolic network and cell fate determination. To deal with the unavoidable DNA damage caused by either endogenous or exogenous stresses, the cells need to reshape the gene expression profile to allow efficient transcription and translation of DDR‐responsive messenger RNAs (mRNAs) and to repress the nonessential mRNAs. A predominant method to adjust RNA fate is achieved by modulating the 3′‐end oligo(A) or poly(A) length via the opposing actions of polyadenylation and deadenylation. Poly(A)‐specific ribonuclease (PARN) and the carbon catabolite repressor 4 (CCR4)‐Not complex, the major executors of deadenylation, are indispensable to DDR and genomic integrity in eukaryotic cells. PARN modulates cell cycle progression by regulating the stabilities of mRNAs and microRNA (miRNAs) involved in the p53 pathway and contributes to genomic stability by affecting the biogenesis of noncoding RNAs including miRNAs and telomeric RNA. The CCR4‐Not complex is involved in diverse pathways of DDR including transcriptional regulation, signaling pathways, mRNA stabilities, translation regulation, and protein degradation. The RNA targets of deadenylases are tuned by the DDR signaling pathways, while in turn the deadenylases can regulate the levels of DNA damage‐responsive proteins. The mutual feedback between deadenylases and the DDR signaling pathways allows the cells to precisely control DDR by dynamically adjusting the levels of sensors and effectors of the DDR signaling pathways. Here, the diverse functions of deadenylases in DDR are summarized and the underlying mechanisms are proposed according to recent findings. This article is categorized under: RNA Processing > 3' End Processing RNA in Disease and Development > RNA in Disease RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms

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“…In recent years, numerous yeast proteins have been discovered as RBFs (e.g., Fujiyama-Nakamura et al, 2009 ; van Tran et al, 2019 ) whose presence in the archaea has not been tested in a comprehensive screen, thus far. Moreover, structure- and mass spectrometry-based approaches have shed light on the order of selected events during the assembly process and the identity of the participating proteins (see for example, Wu et al, 2016 ; Barandun et al, 2017 ; Kater et al, 2017 ; Sanghai et al, 2018 ; Klingauf-Nerurkar et al, 2020 ; Liang et al, 2020 ; Nieto et al, 2020 ). This resource, which provides an excellent basis for identifying functional sub-networks shared between eukaryotes and archaea, is largely untapped.…”

Section: Introductionmentioning

confidence: 99%

Tracing Eukaryotic Ribosome Biogenesis Factors Into the Archaeal Domain Sheds Light on the Evolution of Functional Complexity

et al. 2021

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Ribosome assembly is an essential and carefully choreographed cellular process. In eukaryotes, several 100 proteins, distributed across the nucleolus, nucleus, and cytoplasm, co-ordinate the step-wise assembly of four ribosomal RNAs (rRNAs) and approximately 80 ribosomal proteins (RPs) into the mature ribosomal subunits. Due to the inherent complexity of the assembly process, functional studies identifying ribosome biogenesis factors and, more importantly, their precise functions and interplay are confined to a few and very well-established model organisms. Although best characterized in yeast (Saccharomyces cerevisiae), emerging links to disease and the discovery of additional layers of regulation have recently encouraged deeper analysis of the pathway in human cells. In archaea, ribosome biogenesis is less well-understood. However, their simpler sub-cellular structure should allow a less elaborated assembly procedure, potentially providing insights into the functional essentials of ribosome biogenesis that evolved long before the diversification of archaea and eukaryotes. Here, we use a comprehensive phylogenetic profiling setup, integrating targeted ortholog searches with automated scoring of protein domain architecture similarities and an assessment of when search sensitivity becomes limiting, to trace 301 curated eukaryotic ribosome biogenesis factors across 982 taxa spanning the tree of life and including 727 archaea. We show that both factor loss and lineage-specific modifications of factor function modulate ribosome biogenesis, and we highlight that limited sensitivity of the ortholog search can confound evolutionary conclusions. Projecting into the archaeal domain, we find that only few factors are consistently present across the analyzed taxa, and lineage-specific loss is common. While members of the Asgard group are not special with respect to their inventory of ribosome biogenesis factors (RBFs), they unite the highest number of orthologs to eukaryotic RBFs in one taxon. Using large ribosomal subunit maturation as an example, we demonstrate that archaea pursue a simplified version of the corresponding steps in eukaryotes. Much of the complexity of this process evolved on the eukaryotic lineage by the duplication of ribosomal proteins and their subsequent functional diversification into ribosome biogenesis factors. This highlights that studying ribosome biogenesis in archaea provides fundamental information also for understanding the process in eukaryotes.

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Identification of distinct maturation steps involved in human 40S ribosomal subunit biosynthesis

Cited by 22 publications

References 52 publications

RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit

RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit

Diverse functions of deadenylases in DNA damage response and genomic integrity

Tracing Eukaryotic Ribosome Biogenesis Factors Into the Archaeal Domain Sheds Light on the Evolution of Functional Complexity

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