1. Cell Biology

Autophagy-dependent rRNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development

  1. Yubing Liu
  2. Wei Zou
  3. Peiguo Yang
  4. Li Wang
  5. Yan Ma
  6. Hong Zhang
  7. Xiaochen Wang  Is a corresponding author
  1. Peking University, China
  2. National Institute of Biological Sciences, China
  3. Chinese Academy of Sciences, China
https://doi.org/10.7554/eLife.36588
Share this article
Cite this article
  1. Yubing Liu
  2. Wei Zou
  3. Peiguo Yang
  4. Li Wang
  5. Yan Ma
  6. Hong Zhang
  7. Xiaochen Wang
(2018)
Autophagy-dependent rRNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development
eLife 7:e36588.
https://doi.org/10.7554/eLife.36588
  2. Download BibTeX
  3. Download .RIS

Abstract

Ribosome degradation through the autophagy-lysosome pathway is crucial for cell survival during nutrient starvation, but whether it occurs under normal growth conditions and contributes to animal physiology remains unaddressed. In this study, we identified RNST-2, a C. elegans T2 family endoribonuclease, as the key enzyme that degrades ribosomal RNA in lysosomes. We found that loss of rnst-2 causes accumulation of rRNA and ribosomal proteins in enlarged lysosomes and both phenotypes are suppressed by blocking autophagy, which indicates that RNST-2 mediates autophagic degradation of ribosomal RNA in lysosomes. rnst-2(lf) mutants are defective in embryonic and larval development and are short-lived. Remarkably, simultaneous loss of RNST-2 and de novo synthesis of pyrimidine nucleotides leads to complete embryonic lethality, which is suppressed by supplements of uridine or cytidine. Our study reveals an essential role of autophagy-dependent degradation of ribosomal RNA in maintaining nucleotide homeostasis during animal development.

Data availability

All data generated or analyses during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Yubing Liu

    Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Wei Zou

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Peiguo Yang

    National Laboratory of Biomacromolecules, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Li Wang

    National Laboratory of Biomacromolecules, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Yan Ma

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Hong Zhang

    National Laboratory of Biomacromolecules, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Xiaochen Wang

    National Laboratory of Biomacromolecules, Chinese Academy of Sciences, Beijing, China
    For correspondence
    wangxiaochen@ibp.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4344-0925

Funding

Ministry of Science and Technology of the People's Republic of China

  • Xiaochen Wang

National Science Foundation of China

  • Xiaochen Wang

Chinese Academy of Sciences

  • Xiaochen Wang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2018, Liu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,724
    views
  • 590
    downloads
  • 42
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Yubing Liu
  2. Wei Zou
  3. Peiguo Yang
  4. Li Wang
  5. Yan Ma
  6. Hong Zhang
  7. Xiaochen Wang
(2018)
Autophagy-dependent rRNA degradation is essential for maintaining nucleotide homeostasis during C. elegans development
eLife 7:e36588.
https://doi.org/10.7554/eLife.36588

Share this article

https://doi.org/10.7554/eLife.36588

Categories and tags

Research organism

Further reading

    1. Cancer Biology
    2. Cell Biology

    Plectin-mediated cytoskeletal crosstalk as a target for inhibition of hepatocellular carcinoma growth and metastasis

    Zuzana Outla, Gizem Oyman-Eyrilmez ... Martin Gregor
    Research Article

    The most common primary malignancy of the liver, hepatocellular carcinoma (HCC), is a heterogeneous tumor entity with high metastatic potential and complex pathophysiology. Increasing evidence suggests that tissue mechanics plays a critical role in tumor onset and progression. Here, we show that plectin, a major cytoskeletal crosslinker protein, plays a crucial role in mechanical homeostasis and mechanosensitive oncogenic signaling that drives hepatocarcinogenesis. Our expression analyses revealed elevated plectin levels in liver tumors, which correlated with poor prognosis for HCC patients. Using autochthonous and orthotopic mouse models we demonstrated that genetic and pharmacological inactivation of plectin potently suppressed the initiation and growth of HCC. Moreover, plectin targeting potently inhibited the invasion potential of human HCC cells and reduced their metastatic outgrowth in the lung. Proteomic and phosphoproteomic profiling linked plectin-dependent disruption of cytoskeletal networks to attenuation of oncogenic FAK, MAPK/Erk, and PI3K/Akt signatures. Importantly, by combining cell line-based and murine HCC models, we show that plectin inhibitor plecstatin-1 (PST) is well-tolerated and potently inhibits HCC progression. In conclusion, our study demonstrates that plectin-controlled cytoarchitecture is a key determinant of HCC development and suggests that pharmacologically induced disruption of mechanical homeostasis may represent a new therapeutic strategy for HCC treatment.

    1. Cell Biology
    2. Stem Cells and Regenerative Medicine

    Single-nucleus transcriptomics reveal the cytological mechanism of conjugated linoleic acids in regulating intramuscular fat deposition

    Liyi Wang, Shiqi Liu ... Tizhong Shan
    Research Article

    Conjugated linoleic acids (CLAs) can serve as a nutritional intervention to regulate quality, function, and fat infiltration in skeletal muscles, but the specific cytological mechanisms remain unknown. Here, we applied single-nucleus RNA-sequencing (snRNA-seq) to characterize the cytological mechanism of CLAs regulates fat infiltration in skeletal muscles based on pig models. We investigated the regulatory effects of CLAs on cell populations and molecular characteristics in pig muscles and found CLAs could promote the transformation of fast glycolytic myofibers into slow oxidative myofibers. We also observed three subpopulations including SCD+/DGAT2+, FABP5+/SIAH1+, and PDE4D+/PDE7B+ subclusters in adipocytes and CLAs could increase the percentage of SCD+/DGAT2+ adipocytes. RNA velocity analysis showed FABP5+/SIAH1+ and PDE4D+/PDE7B+ adipocytes could differentiate into SCD+/DGAT2+ adipocytes. We further verified the differentiated trajectory of mature adipocytes and identified PDE4D+/PDE7B+ adipocytes could differentiate into SCD+/DGAT2+ and FABP5+/SIAH1+ adipocytes by using high intramuscular fat (IMF) content Laiwu pig models. The cell-cell communication analysis identified the interaction network between adipocytes and other subclusters such as fibro/adipogenic progenitors (FAPs). Pseudotemporal trajectory analysis and RNA velocity analysis also showed FAPs could differentiate into PDE4D+/PDE7B+ preadipocytes and we discovered the differentiated trajectory of preadipocytes into mature adipocytes. Besides, we found CLAs could promote FAPs differentiate into SCD+/DGAT2+ adipocytes via inhibiting c-Jun N-terminal kinase (JNK) signaling pathway in vitro. This study provides a foundation for regulating fat infiltration in skeletal muscles by using nutritional strategies and provides potential opportunities to serve pig as an animal model to study human fat infiltrated diseases.

    1. Cell Biology
    2. Medicine

    PCBP2 as an intrinsic agi ng factor regulates the senescence of hBMSCs through the ROS-FGF2 signaling axis

    Pengbo Chen, Bo Li ... Xinfeng Zheng
    Research Article

    Background:

    It has been reported that loss of PCBP2 led to increased reactive oxygen species (ROS) production and accelerated cell aging. Knockdown of PCBP2 in HCT116 cells leads to significant downregulation of fibroblast growth factor 2 (FGF2). Here, we tried to elucidate the intrinsic factors and potential mechanisms of bone marrow mesenchymal stromal cells (BMSCs) aging from the interactions among PCBP2, ROS, and FGF2.

    Methods:

    Unlabeled quantitative proteomics were performed to show differentially expressed proteins in the replicative senescent human bone marrow mesenchymal stromal cells (RS-hBMSCs). ROS and FGF2 were detected in the loss-and-gain cell function experiments of PCBP2. The functional recovery experiments were performed to verify whether PCBP2 regulates cell function through ROS/FGF2-dependent ways.

    Results:

    PCBP2 expression was significantly lower in P10-hBMSCs. Knocking down the expression of PCBP2 inhibited the proliferation while accentuated the apoptosis and cell arrest of RS-hBMSCs. PCBP2 silence could increase the production of ROS. On the contrary, overexpression of PCBP2 increased the viability of both P3-hBMSCs and P10-hBMSCs significantly. Meanwhile, overexpression of PCBP2 led to significantly reduced expression of FGF2. Overexpression of FGF2 significantly offset the effect of PCBP2 overexpression in P10-hBMSCs, leading to decreased cell proliferation, increased apoptosis, and reduced G0/G1 phase ratio of the cells.

    Conclusions:

    This study initially elucidates that PCBP2 as an intrinsic aging factor regulates the replicative senescence of hBMSCs through the ROS-FGF2 signaling axis.

    Funding:

    This study was supported by the National Natural Science Foundation of China (82172474).