1. Cell Biology
Download icon

Multiplexed mRNA assembly into ribonucleoprotein particles plays an operon-like role in the control of yeast cell physiology

  1. Rohini R Nair
  2. Dimitry Zabezhinsky
  3. Rita Gelin-Licht
  4. Brian J Haas
  5. Michael CA Dyhr
  6. Hannah S Sperber
  7. Chad Nusbaum
  8. Jeffrey E Gerst  Is a corresponding author
  1. Weizmann Institute of Science, Israel
  2. Broad Institute of MIT and Harvard, United States
Research Article
  • Cited 0
  • Views 304
  • Annotations
Cite this article as: eLife 2021;10:e66050 doi: 10.7554/eLife.66050
Voice your concerns about research culture and research communication: Have your say in our 7th annual survey.

Abstract

Prokaryotes utilize polycistronic messages (operons) to co-translate proteins involved in the same biological processes. Whether eukaryotes achieve similar regulation by selectively assembling and translating monocistronic messages derived from different chromosomes is unknown. We employed transcript-specific RNA pulldowns and RNA-seq/RT-PCR to identify yeast mRNAs that co-precipitate as ribonucleoprotein (RNP) complexes. Consistent with the hypothesis of eukaryotic RNA operons, mRNAs encoding components of the mating pathway, heat shock proteins, and mitochondrial outer membrane proteins multiplex in trans, forming discrete mRNP complexes (called transperons). Chromatin-capture and allele tagging experiments reveal that genes encoding multiplexed mRNAs physically interact, thus, RNA assembly may result from co-regulated gene expression. Transperon assembly and function depends upon histone H4 and depletion leads to defects in RNA multiplexing, decreased pheromone responsiveness and mating, and increased heat shock sensitivity. We propose that intergenic associations and non-canonical histone H4 functions contribute to transperon formation in eukaryotic cells and regulate cell physiology.

Data availability

All data is available within the text, figures, and tables of the manuscript

Article and author information

Author details

  1. Rohini R Nair

    Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    No competing interests declared.
  2. Dimitry Zabezhinsky

    Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    No competing interests declared.
  3. Rita Gelin-Licht

    Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    No competing interests declared.
  4. Brian J Haas

    Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States
    Competing interests
    No competing interests declared.
  5. Michael CA Dyhr

    Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    No competing interests declared.
  6. Hannah S Sperber

    Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    No competing interests declared.
  7. Chad Nusbaum

    Technology Labs, Broad Institute of MIT and Harvard, Cambridge, MA, United States
    Competing interests
    Chad Nusbaum, Chad Nusbaum is affiliated with Cellarity Inc. The author has no financial interests to declare..
  8. Jeffrey E Gerst

    Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    jeffrey.gerst@weizmann.ac.il
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8411-6881

Funding

German-Israeli Foundation for Scientific Research and Development (I-1190-96.13/2012)

  • Jeffrey E Gerst

Minerva Foundation (711130)

  • Jeffrey E Gerst

Astrachan Olga Klein Fund, Weizmann Institute

  • Jeffrey E Gerst

National Institutes of Health (NHGRI U54HG00306)

  • Chad Nusbaum

Israel Council of Higher Education

  • Rita Gelin-Licht

Israel Science Foundation (578/18)

  • Jeffrey E Gerst

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

Reviewing Editor

  1. Karsten Weis, ETH Zurich, Switzerland

Publication history

  1. Received: December 23, 2020
  2. Accepted: May 2, 2021
  3. Accepted Manuscript published: May 4, 2021 (version 1)

Copyright

© 2021, Nair 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

  • 304
    Page views
  • 36
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

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

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

Further reading

    1. Cell Biology
    Na Li et al.
    Research Article Updated

    Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adiponectin on promoting healthspan and lifespan remain unexplored. Here, we are using an adiponectin null mouse and a transgenic adiponectin overexpression model. We directly assessed the effects of circulating adiponectin on the aging process and found that adiponectin null mice display exacerbated age-related glucose and lipid metabolism disorders. Moreover, adiponectin null mice have a significantly shortened lifespan on both chow and high-fat diet. In contrast, a transgenic mouse model with elevated circulating adiponectin levels has a dramatically improved systemic insulin sensitivity, reduced age-related tissue inflammation and fibrosis, and a prolonged healthspan and median lifespan. These results support a role of adiponectin as an essential regulator for healthspan and lifespan.

    1. Cell Biology
    2. Structural Biology and Molecular Biophysics
    Axel F Brilot et al.
    Research Article

    Microtubule (MT) nucleation is regulated by the γ-tubulin ring complex (γTuRC), conserved from yeast to humans. In Saccharomyces cerevisiae, γTuRC is composed of seven identical γ-tubulin small complex (γTuSC) sub-assemblies, which associate helically to template MT growth. γTuRC assembly provides a key point of regulation for the MT cytoskeleton. Here, we combine crosslinking mass spectrometry, X-ray crystallography, and cryo-EM structures of both monomeric and dimeric γTuSCs, and open and closed helical γTuRC assemblies in complex with Spc110p to elucidate the mechanisms of γTuRC assembly. γTuRC assembly is substantially aided by the evolutionarily conserved CM1 motif in Spc110p spanning a pair of adjacent γTuSCs. By providing the highest resolution and most complete views of any γTuSC assembly, our structures allow phosphorylation sites to be mapped, surprisingly suggesting that they are mostly inhibitory. A comparison of our structures with the CM1 binding site in the human γTuRC structure at the interface between GCP2 and GCP6 allows for the interpretation of significant structural changes arising from CM1 helix binding to metazoan γTuRC.