Ribosomal Protein L10: From Function to Dysfunction

Pollutri, Daniela; Penzo, Marianna

doi:10.3390/cells9112503

Cited by 21 publications

(19 citation statements)

References 87 publications

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“…Similarly, structural analysis of somatic cancer-associated RP mutations, including the mutation hotspots in RPL10 and RPS15 revealed that these RP mutations are localized in the regions associated with the catalytic core of ribosome, consistent with their influence on mRNA translation and thus global protein synthesis. 197,224 An altered translation pattern in cancer cells with RP mutations may promote oncogenic protein synthesis. For instance, the T-ALL-associated RPL10-R98S mutation protects leukemia cell survival via specific upregulation of IRES-dependent translation of the antiapoptotic molecule BCL2.…”

Section: The Molecular Basis Of Ribosomopathiesmentioning

confidence: 99%

Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy

Kang

Brajanovski

Chan

et al. 2021

Sig Transduct Target Ther

225

127

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Ribosome biogenesis and protein synthesis are fundamental rate-limiting steps for cell growth and proliferation. The ribosomal proteins (RPs), comprising the structural parts of the ribosome, are essential for ribosome assembly and function. In addition to their canonical ribosomal functions, multiple RPs have extra-ribosomal functions including activation of p53-dependent or p53-independent pathways in response to stress, resulting in cell cycle arrest and apoptosis. Defects in ribosome biogenesis, translation, and the functions of individual RPs, including mutations in RPs have been linked to a diverse range of human congenital disorders termed ribosomopathies. Ribosomopathies are characterized by tissue-specific phenotypic abnormalities and higher cancer risk later in life. Recent discoveries of somatic mutations in RPs in multiple tumor types reinforce the connections between ribosomal defects and cancer. In this article, we review the most recent advances in understanding the molecular consequences of RP mutations and ribosomal defects in ribosomopathies and cancer. We particularly discuss the molecular basis of the transition from hypo- to hyper-proliferation in ribosomopathies with elevated cancer risk, a paradox termed “Dameshek’s riddle.” Furthermore, we review the current treatments for ribosomopathies and prospective therapies targeting ribosomal defects. We also highlight recent advances in ribosome stress-based cancer therapeutics. Importantly, insights into the mechanisms of resistance to therapies targeting ribosome biogenesis bring new perspectives into the molecular basis of cancer susceptibility in ribosomopathies and new clinical implications for cancer therapy.

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Section: The Molecular Basis Of Ribosomopathiesmentioning

confidence: 99%

Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy

Kang

Brajanovski

Chan

et al. 2021

Sig Transduct Target Ther

225

127

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“…Addition of the transcriptional inhibitor actinomycin D resulted in a loss of the typical nucleolar fluorescence, presumably caused by a stop of the production of pre-ribosomal particles. A pull-down experiment demonstrated that the labelled eIF6 was contained in molecular aggregates that comprised also the ribosomal protein Rpl10, an established component of pre-60S particles(reviewed by 42 ). Incubation with LMB, an inhibitor of pre-60S nuclear export by blocking Crm1, resulted accordingly in an increase of nuclear fluorescence.…”

Section: Discussionmentioning

confidence: 99%

Nuclear export of the pre-60S ribosomal subunit through single nuclear pores observed in real time

Ruland

Krueger

Doerner

et al. 2021

Preprint

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Ribosomal subunit biogenesis within mammalian cells initiates in the nucleolus with the assembly of a 90S precursor particle, which is subsequently split into the pre-40S and pre-60S subunits. During further processing steps, pre-ribosomal subunits are loaded with export receptors, which enables their passage through the pore complexes (NPCs) into the cytoplasm. Here export factors are released and both subunits can form a mature ribosome. Ribosomal biogenesis has been studied in great detail by biochemical, genetic and electron microscopic approaches, however, until now live cell data on the in vivo kinetics are still missing. We analysed export kinetics of the large ribosomal subunit (pre-60S particle) through single NPCs in living human cells. To assess the in vivo dynamics of this process, we established a stable cell line co-expressing Halo-tagged eIF6 and GFP-fused NTF2 to simultaneously label ribosomal 60S subunits (eIF6) and NPCs (NTF2). By combining single molecule tracking and super resolution confocal microscopy in a highly customized microscopic setup, we visualized the dynamics of single pre-60S particles during the interaction with and export through single NPCs. In this way we obtained unprecedented insights into this key cellular process. Our results revealed that for export events, maximum particle accumulation is found in the centre of the pore, while unsuccessful export terminates within the nuclear basket. The export process takes place with a single rate limiting step and an export dwell time of ~24 milliseconds. Only about 1/3 of attempted export events were successful. Given the molecular mass of the pre-60S particles our results show that the mass flux through a single NPC can reach up to ~125 MDa s-1 in vivo.

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“…In human, RPL10 is also known as the QM protein, which could be translocated from the cytoplasm to the nucleus promoted by presenilin 1 (PS1). The nuclear QM could bind to c-Jun protein as a negative regulator of the latter (Imafuku et al, 1999;Pollutri and Penzo, 2020). There are three paralogous genes encoding RPL10 in the Arabidopsis genome [RPL10A (At1G14320), RPL10B (AT1G26910), and RPL10C (AT1G66580)], with these genes sharing 90-95% sequence identity (Barakat et al, 2001).…”

Section: Extraribosomal Functions Of Rp Genes In Plants Free Rpl10a Involves In Transcriptional Regulations Of Certain Genesmentioning

confidence: 99%

Extraribosomal Functions of Cytosolic Ribosomal Proteins in Plants

Xiong

Lan²,

Mo³

2021

Front. Plant Sci.

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Ribosomes are basic translational machines in all living cells. The plant cytosolic ribosome is composed of four rRNAs and approximately 81 ribosomal proteins (RPs). In addition to the fundamental functions of RPs in the messenger RNA decoding process as well as in polypeptide synthesis and ribosome assembly, extraribosomal functions of RPs that occur in the absence of the ribosome have been proposed and studied with respect to RPs’ ability to interact with RNAs and non-ribosomal proteins. In a few cases, extraribosomal functions of several RPs have been demonstrated with solid evidences in plants, including microRNA biogenesis, anti-virus defenses, and plant immunity, which have fascinated biologists. We believe that the widespread duplication of RP genes in plants may increase the potential of extraribosomal functions of RPs and more extraribosomal functions of plant RPs will be discovered in the future. In this article we review the current knowledge concerning the extraribosomal functions of RPs in plants and described the prospects for future research in this fascinating area.

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Ribosomal Protein L10: From Function to Dysfunction

Cited by 21 publications

References 87 publications

Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy

Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy

Nuclear export of the pre-60S ribosomal subunit through single nuclear pores observed in real time

Extraribosomal Functions of Cytosolic Ribosomal Proteins in Plants

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