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Updated: May 18, 2026

Identifying the Binding Proteins of Small Ligands with the Differential Radial Capillary Action of Ligand Assay (DRaCALA)
Published on: March 19, 2021
POS-1 and GLD-1 repress glp-1 translation through a conserved binding-site cluster
1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Abstract:
RNA-binding proteins (RBPs) coordinate cell fate specification and differentiation in a variety of systems. RNA regulation is critical during oocyte development and early embryogenesis, in which RBPs control expression from maternal mRNAs encoding key cell fate determinants. The Caenorhabditis elegans Notch homologue glp-1 coordinates germline progenitor cell proliferation and anterior fate specification in embryos. A network of sequence-specific RBPs is required to pattern GLP-1 translation. Here, we map the cis-regulatory elements that guide glp-1 regulation by the CCCH-type tandem zinc finger protein POS-1 and the STAR-domain protein GLD-1. Our results demonstrate that both proteins recognize the glp-1 3' untranslated region (UTR) through adjacent, overlapping binding sites and that POS-1 binding excludes GLD-1 binding. Both factors are required to repress glp-1 translation in the embryo, suggesting that they function in parallel regulatory pathways. It is intriguing that two equivalent POS-1-binding sites are present in the glp-1 3' UTR, but only one, which overlaps with a translational derepression element, is functional in vivo. We propose that POS-1 regulates glp-1 mRNA translation by blocking access of other RBPs to a key regulatory sequence.
Insights
RNA-binding proteins POS-1 and GLD-1 regulate early embryo development by controlling the translation of the glp-1 gene. They bind overlapping sites in the glp-1 3' untranslated region to repress gene expression.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- RNA-binding proteins (RBPs) are crucial for cell fate specification and differentiation.
- Maternal mRNA regulation by RBPs is essential during oocyte development and early embryogenesis.
- The Caenorhabditis elegans glp-1 gene, a Notch homologue, is vital for germline progenitor proliferation and anterior fate specification.
Purpose of the Study:
- To map cis-regulatory elements controlling glp-1 translation.
- To investigate the roles of RBPs POS-1 and GLD-1 in glp-1 regulation.
- To understand the mechanism of translational control of glp-1 during embryogenesis.
Main Methods:
- Mapping cis-regulatory elements in the glp-1 3' untranslated region (UTR).
- Analyzing binding sites and interactions of POS-1 and GLD-1 on glp-1 mRNA.
- Investigating the in vivo function of POS-1 binding sites.
Main Results:
- POS-1 and GLD-1 recognize adjacent, overlapping binding sites within the glp-1 3' UTR.
- POS-1 binding inhibits GLD-1 binding.
- Both POS-1 and GLD-1 are required to repress glp-1 translation in embryos, acting in parallel pathways.
- Only one of two potential POS-1 binding sites in the glp-1 3' UTR is functional in vivo, overlapping a translational derepression element.
Conclusions:
- POS-1 and GLD-1 function in parallel pathways to repress glp-1 translation during early embryogenesis.
- POS-1 likely regulates glp-1 mRNA translation by sterically hindering other RBPs from accessing critical regulatory sequences.
- The specific binding and functional activity of POS-1 sites highlight intricate regulatory mechanisms in early development.
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