The TRIM-NHL protein NHL-2 is a co-factor in the nuclear and somatic RNAi pathways in C. elegans
- Federation University, Australia
- University of Massachusetts Medical School, United States
- Monash University, Australia
- University of Toronto, Canada
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, United States
Abstract
Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 is a bona fide RNA binding protein and, along with RNA-seq data point to a small RNA independent role for NHL-2 in regulating transcripts at the level of RNA stability. Collectively, our data implicate NHL-2 as an essential hub of gene regulatory activity in both the germline and soma.
Data availability
All small RNA and mRNA Illumina sequencing data have been submitted to the NCBI's Sequence Read Archive (SRA), and are included under project accession number SRP115391.
-
Caenorhabditis elegans Raw sequences reads NHL-2, Aug 12'17NCBI Sequence Read Archive, SRP115391.
Article and author information
Author details
Funding
National Health and Medical Research Council (606575)
- Peter R Boag
Canada Research Chairs (MOP-274660)
- Julie M Claycomb
Canadian Institutes of Health Research (MOP-125894)
- Quaid D Morris
- Timothy R Hughes
Connaught Fund
- Julie M Claycomb
National Institutes of Health (HD078253)
- Zhiping Weng
Canada Research Chairs (CAP- 783 262134)
- Julie M Claycomb
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States
Publication history
- Received: January 30, 2018
- Accepted: December 20, 2018
- Accepted Manuscript published: December 21, 2018 (version 1)
- Version of Record published: January 29, 2019 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 2,055
- Page views
-
- 283
- Downloads
-
- 7
- 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)
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)
The TRIM-NHL protein NHL-2 is a co-factor in the nuclear and somatic RNAi pathways in C. elegans
eLife 7:e35478.
https://doi.org/10.7554/eLife.35478
Further reading
-
- Chromosomes and Gene Expression
An evolutionary perspective enhances our understanding of biological mechanisms. Comparison of sex determination and X-chromosome dosage compensation mechanisms between the closely related nematode species C. briggsae (Cbr) and C. elegans (Cel) revealed that the genetic regulatory hierarchy controlling both processes is conserved, but the X-chromosome target specificity and mode of binding for the specialized condensin dosage compensation complex (DCC) controlling X expression have diverged. We identified two motifs within Cbr DCC recruitment sites that are highly enriched on X: 13-bp MEX and 30-bp MEX II. Mutating either MEX or MEX II in an endogenous recruitment site with multiple copies of one or both motifs reduced binding, but only removing all motifs eliminated binding in vivo. Hence, DCC binding to Cbr recruitment sites appears additive. In contrast, DCC binding to Cel recruitment sites is synergistic: mutating even one motif in vivo eliminated binding. Although all X-chromosome motifs share the sequence CAGGG, they have otherwise diverged so that a motif from one species cannot function in the other. Functional divergence was demonstrated in vivo and in vitro. A single nucleotide position in Cbr MEX can determine whether Cel DCC binds. This rapid divergence of DCC target specificity could have been an important factor in establishing reproductive isolation between nematode species and contrasts dramatically with conservation of target specificity for X-chromosome dosage compensation across Drosophila species and for transcription factors controlling developmental processes such as body-plan specification from fruit flies to mice.
-
- Chromosomes and Gene Expression
- Plant Biology
A well-established model for how plants start the process of flowering in periods of cold weather may need revisiting.
