1. Chromosomes and Gene Expression

A SUMO E3 ligase promotes long non-coding RNA transcription to regulate small RNA-directed DNA elimination

  1. Salman Shehzada
  2. Tomoko Noto
  3. Julie Saksouk
  4. Kazufumi Mochizuki  Is a corresponding author
  1. University of Montpellier, CNRS, France
https://doi.org/10.7554/eLife.95337
Share this article
Cite this article
  1. Salman Shehzada
  2. Tomoko Noto
  3. Julie Saksouk
  4. Kazufumi Mochizuki
(2024)
A SUMO E3 ligase promotes long non-coding RNA transcription to regulate small RNA-directed DNA elimination
eLife 13:e95337.
https://doi.org/10.7554/eLife.95337
  2. Download BibTeX
  3. Download .RIS

Abstract

Small RNAs target their complementary chromatin regions for gene silencing through nascent long non-coding RNAs (lncRNAs). In the ciliated protozoan Tetrahymena, the interaction between Piwi-associated small RNAs (scnRNAs) and the nascent lncRNA transcripts from the somatic genome has been proposed to induce target-directed small RNA degradation (TDSD), and scnRNAs not targeted for TDSD later target the germline-limited sequences for programmed DNA elimination. In this study, we show that the SUMO E3 ligase Ema2 is required for the accumulation of lncRNAs from the somatic genome and thus for TDSD and completing DNA elimination to make viable sexual progeny. Ema2 interacts with the SUMO E2 conjugating enzyme Ubc9 and enhances SUMOylation of the transcription regulator Spt6. We further show that Ema2 promotes the association of Spt6 and RNA polymerase II with chromatin. These results suggest that Ema2-directed SUMOylation actively promotes lncRNA transcription, which is a prerequisite for communication between the genome and small RNAs.

Data availability

Data DepositionThe small RNA sequencing data have been deposited in the Gene Expression Omnibus (GEO) database, https://www.ncbi.nlm.nih.gov/geo (accession no. GSE243435). The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the MassIVE partner repository (https://massive.ucsd.edu/) with the database identifier MSV000092977.

The following data sets were generated

Article and author information

Author details

  1. Salman Shehzada

    Institute of Human Genetics, University of Montpellier, CNRS, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4218-7622

  2. Tomoko Noto

    Institute of Human Genetics, University of Montpellier, CNRS, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.

  3. Julie Saksouk

    Institute of Human Genetics (IGH), University of Montpellier, CNRS, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1885-1762

  4. Kazufumi Mochizuki

    Institute of Human Genetics, University of Montpellier, CNRS, Montpellier, France
    For correspondence
    kazufumi.mochizuki@cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7987-9852

Funding

Agence Nationale de la Recherche (ANR-10-INBS-04)

  • Kazufumi Mochizuki

Agence Nationale de la Recherche (ANR-10-LABX-12-01)

  • Kazufumi Mochizuki

Agence Nationale de la Recherche (ANR-16-ACHN-0017)

  • Kazufumi Mochizuki

Fondation pour la Recherche Médicale

  • Salman Shehzada

Foundation Recherche Médicale (EQU202203014651)

  • Kazufumi Mochizuki

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

Copyright

© 2024, Shehzada 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

  • 1,126
    views
  • 309
    downloads
  • 3
    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. Salman Shehzada
  2. Tomoko Noto
  3. Julie Saksouk
  4. Kazufumi Mochizuki
(2024)
A SUMO E3 ligase promotes long non-coding RNA transcription to regulate small RNA-directed DNA elimination
eLife 13:e95337.
https://doi.org/10.7554/eLife.95337

Share this article

https://doi.org/10.7554/eLife.95337

Categories and tags

Further reading

    1. Chromosomes and Gene Expression
    2. Evolutionary Biology

    The domesticated transposon protein L1TD1 associates with its ancestor L1 ORF1p to promote LINE-1 retrotransposition

    Gülnihal Kavaklioglu, Alexandra Podhornik ... Christian Seiser
    Research Article

    Repression of retrotransposition is crucial for the successful fitness of a mammalian organism. The domesticated transposon protein L1TD1, derived from LINE-1 (L1) ORF1p, is an RNA-binding protein that is expressed only in some cancers and early embryogenesis. In human embryonic stem cells, it is found to be essential for maintaining pluripotency. In cancer, L1TD1 expression is highly correlative with malignancy progression and as such considered a potential prognostic factor for tumors. However, its molecular role in cancer remains largely unknown. Our findings reveal that DNA hypomethylation induces the expression of L1TD1 in HAP1 human tumor cells. L1TD1 depletion significantly modulates both the proteome and transcriptome and thereby reduces cell viability. Notably, L1TD1 associates with L1 transcripts and interacts with L1 ORF1p protein, thereby facilitating L1 retrotransposition. Our data suggest that L1TD1 collaborates with its ancestral L1 ORF1p as an RNA chaperone, ensuring the efficient retrotransposition of L1 retrotransposons, rather than directly impacting the abundance of L1TD1 targets. In this way, L1TD1 might have an important role not only during early development but also in tumorigenesis.

    1. Chromosomes and Gene Expression

    Nuclear Argonaute protein NRDE-3 switches small RNA partners during embryogenesis to mediate temporal-specific gene regulatory activity

    Shihui Chen, Carolyn Marie Phillips
    Research Article

    RNA interference (RNAi) is a conserved pathway that utilizes Argonaute proteins and their associated small RNAs to exert gene regulatory function on complementary transcripts. While the majority of germline-expressed RNAi proteins reside in perinuclear germ granules, it is unknown whether and how RNAi pathways are spatially organized in other cell types. Here, we find that the small RNA biogenesis machinery is spatially and temporally organized during Caenorhabditis elegans embryogenesis. Specifically, the RNAi factor, SIMR-1, forms visible concentrates during mid-embryogenesis that contain an RNA-dependent RNA polymerase, a poly-UG polymerase, and the unloaded nuclear Argonaute protein, NRDE-3. Curiously, coincident with the appearance of the SIMR granules, the small RNAs bound to NRDE-3 switch from predominantly CSR-class 22G-RNAs to ERGO-dependent 22G-RNAs. NRDE-3 binds ERGO-dependent 22G-RNAs in the somatic cells of larvae and adults to silence ERGO-target genes; here we further demonstrate that NRDE-3-bound, CSR-class 22G-RNAs repress transcription in oocytes. Thus, our study defines two separable roles for NRDE-3, targeting germline-expressed genes during oogenesis to promote global transcriptional repression, and switching during embryogenesis to repress recently duplicated genes and retrotransposons in somatic cells, highlighting the plasticity of Argonaute proteins and the need for more precise temporal characterization of Argonaute-small RNA interactions.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Transcription: The plusses and minuses of DNA torsion

    Steven Henikoff, David L Levens
    Insight

    A new method for mapping torsion provides insights into the ways that the genome responds to the torsion generated by RNA polymerase II.