Polyribosome and ribonucleoprotein complex redistribution of mRNA induced by GnRH involves both EIF2AK3 and MAPK
Minh-Ha T Do1, Taeshin Kim1, Feng He2
1Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA 92093, United States.
Abstract:
The neuropeptide gonadotropin-releasing hormone stimulates synthesis and secretion of the glycoprotein gonadotropic hormones and activates the unfolded protein response, which causes a transient reduction of endoplasmic reticulum-associated mRNA translation. Hormone-treated cell extracts were fractionated to resolve mRNA in active polyribosomes from mRNA in inactive complexes. Quantitative real-time PCR and expression array analysis were used to determine hormone-induced redistribution of mRNAs between fractions and individual mRNAs were found to be redistributed differentially. Among the affected mRNAs relevant to gonadotropin synthesis, the luteinizing hormone subunit genes Lhb and Cga were enriched in the ribonucleoprotein pool. The MAP kinase phosphatase Dusp1 was enriched in the polyribosome pool. Enrichment of Dusp1 mRNA in the polyribosome pool was independent of the unfolded protein response, sensitive to ERK inhibition, and dependent on the 3'untranslated region. The results show that GnRH exerts translational control to modulate physiologically relevant gene expression through two distinct signaling pathways.
Insights
Gonadotropin-releasing hormone (GnRH) controls gene expression by regulating mRNA translation. This study reveals GnRH uses distinct pathways to modulate luteinizing hormone subunit and Dusp1 mRNA translation.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Gonadotropin-releasing hormone (GnRH) is a key regulator of reproductive function.
- GnRH stimulates gonadotropin synthesis and secretion and activates the unfolded protein response (UPR).
- UPR activation leads to a transient reduction in endoplasmic reticulum-associated mRNA translation.
Purpose of the Study:
- To investigate how GnRH modulates mRNA translation.
- To identify specific genes and signaling pathways involved in GnRH-induced translational control.
- To understand the differential redistribution of mRNAs between active and inactive translation states.
Main Methods:
- Fractionation of hormone-treated cell extracts to separate polysomes and ribonucleoprotein complexes.
- Quantitative real-time PCR and expression array analysis to assess mRNA redistribution.
- Investigating the role of the UPR, ERK signaling, and 3' untranslated regions in mRNA translational control.
Main Results:
- GnRH treatment caused differential redistribution of mRNAs between translation states.
- Luteinizing hormone subunit (Lhb) and common alpha subunit (Cga) mRNAs were enriched in the inactive ribonucleoprotein pool.
- Dusp1 mRNA, encoding MAP kinase phosphatase, was enriched in the active polyribosome pool, independently of the UPR and dependent on its 3' untranslated region and ERK signaling.
Conclusions:
- GnRH exerts translational control over gene expression through at least two distinct signaling pathways.
- Differential mRNA enrichment in polysomes or ribonucleoprotein pools allows for precise regulation of specific gene products.
- These findings provide new insights into the post-transcriptional mechanisms governing reproductive hormone synthesis and signaling.
Related Concept Videos
02:31Nuclear Export of mRNA
02:31Nuclear Export of mRNA
01:34Directing Proteins to the Rough Endoplasmic Reticulum
02:22Regulated mRNA Transport
02:22Regulated mRNA Transport
01:31Regulation of the Unfolded Protein Response