A non-canonical mechanism for Crm1-export cargo complex assembly

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yeon Soo; Faza, Marius B.; Panse, Vikram Govind

doi:10.7554/elife.05745

Cited by 36 publications

(28 citation statements)

References 90 publications

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“…We see at least two plausible scenarios that could explain the accumulation of free 60S subunits without apparent changes in the levels of 40S subunits in PDCD2L-null cells: (i) PDCD2L functions as one of several redundant adaptors that promote the CRM1-mediated nuclear export of pre-40S particles, or (ii) PDCD2L contributes to the export and/or maturation of a subpopulation of 40S ribosomal particles that is involved in a specialized function. The first possibility is supported by evidence showing that Rio2, a conserved ribosome biogenesis factor that binds directly to CRM1 and associates with 40S precursors, promotes pre-40S export in yeast and humans (42,68). Ltv1p and Dim2p, which are the homologs of mammalian hLTV1 and hDIM2/PNO1, respectively, have also been shown to promote pre-40S export in S. cerevisiae and were suggested to be possible adaptors for CRM1-mediated export of 40S precursors (69,70).…”

Section: Discussionmentioning

confidence: 61%

Human PDCD2L Is an Export Substrate of CRM1 That Associates with 40S Ribosomal Subunit Precursors

Landry-Voyer

Bilodeau

Bergeron

et al. 2016

Molecular and Cellular Biology

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c Protein arginine methyltransferase 3 (PRMT3) forms a stable complex with 40S ribosomal protein S2 (RPS2) and contributes to ribosome biogenesis. However, the molecular mechanism by which PRMT3 influences ribosome biogenesis and/or function still remains unclear. Using quantitative proteomics, we identified human programmed cell death 2-like (PDCD2L) as a novel PRMT3-associated protein. Our data suggest that RPS2 promotes the formation of a conserved extraribosomal complex with PRMT3 and PDCD2L. We also show that PDCD2L associates with 40S subunit precursors that contain a 3=-extended form of the 18S rRNA (18S-E pre-rRNA) and several pre-40S maturation factors. PDCD2L shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner using a leucine-rich nuclear export signal that is sufficient to direct the export of a reporter protein. Although PDCD2L is not required for the biogenesis and export of 40S ribosomal subunits, we found that PDCD2L-null cells accumulate free 60S ribosomal subunits, which is indicative of a deficiency in 40S subunit availability. Our data also indicate that PDCD2L and its paralog, PDCD2, function redundantly in 40S ribosomal subunit production. Our findings uncover the existence of an extraribosomal complex consisting of PDCD2L, RPS2, and PRMT3 and support a role for PDCD2L in the late maturation of 40S ribosomal subunits.

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Section: Discussionmentioning

confidence: 61%

Human PDCD2L Is an Export Substrate of CRM1 That Associates with 40S Ribosomal Subunit Precursors

Landry-Voyer

Bilodeau

Bergeron

et al. 2016

Molecular and Cellular Biology

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“…Ribosomal precursor particles are exported from the nucleus to the cytoplasm once they become competent to bind nuclear export factors (Fischer et al 2015;Malyutin et al 2017). If assembly is blocked r-proteins accumulate in the nucleus (Hurt et al 1999;Milkereit et al 2003).…”

Section: Constraining 60s Assembly Inhibits Nuclear Export Of Both Prmentioning

confidence: 99%

The small and large ribosomal subunits depend on each other for stability and accumulation

Rahman

Bommakanti

Shamsuzzaman

et al. 2018

Preprint

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The 1:1 balance between the numbers of large and small ribosomal subunits can be disturbed by mutations that inhibit the assembly of one of the subunits. We have investigated if the cell has mechanisms to counteract an imbalance of subunits. We show that accumulation of 40S subunits stops after abrogating 60S assembly. In contrast, cessation of the 40S pathways does not prevent 60S accumulation, but does, however, lead to fragmentation of the 25S rRNA in 60S subunits. Even though 40S subunits do not accumulate in the absence of 60S assembly, 40S assembly continues, indicating that excess 40S is degraded after assembly. Thus, the cell expends substantial resources in a futile attempt to increase the number of functional 80S ribosomes. We propose that a mechanism for preventing the accumulation of 40S subunits in excess over 60S subunits may have evolved to prevent mRNAs from being tied up in 40S-mRNA translation initiation complexes that cannot be turned into productive translation complexes because of the deficit of 60S subunits.All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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“…Furthermore, it is proposed that recruitment of RanGTP-bound Crm1 to these, or other currently unknown, adaptor proteins may be enhanced by Yrb2, as depletion of this protein causes a strong nuclear accumulation of pre-40S particles and its human homologue (RanBP3) has been implicated in loading Crm1 to other RNP cargos [169,170,171]. Similarly, Slx9 was recently shown to facilitate export of pre-40S complexes by binding to both RanGTP and Rio2 and establishing them in a conformation that promotes recruitment of Crm1 [172].…”

Section: Accepted Manuscriptmentioning

confidence: 96%