Hormone-regulated dynamics of mRNA distribution on ribosomes in Sertoli cells

Leray, X.; Morales, J.; Trefier, A.; Leon, K.; Bourquard, T.; Musnier, A.; Pecnard, E.; Drobecq, L.; Boulben, S.; Azzopardi, N.; Coulaud, R.; Ouchene, H.; Jaszczyszyn, Y.; Reiter, E.; Guillou, F.; Pellissier, L. P.; Poupon, A.; Yvinec, R.; Crepieux, P.

doi:10.1101/2024.12.20.629416

bioRxiv · 10.1101/2024.12.20.629416

Hormone-regulated dynamics of mRNA distribution on ribosomes in Sertoli cells

Leray, X.·Morales, J.·Trefier, A.·Leon, K.·Bourquard, T.·Musnier, A.·Pecnard, E.·Drobecq, L.·Boulben, S.·Azzopardi, N.·Coulaud, R.·Ouchene, H.·Jaszczyszyn, Y.·Reiter, E.·Guillou, F.·Pellissier, L. P.·Poupon, A.·Yvinec, R.·Crepieux, P.

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Abstract

The effects of hormone stimulation on the cell translational profile remain poorly understood. Here, using polysome profiling combined to RNA sequencing, we analyzed the translational response to follicle-stimulating hormone (FSH) of primary rat Sertoli cells, that exhibit an active anabolic activity regulated by reproductive hormones in the male gonad. We first established that mRNA distribution to polysomes follows a bimodal pattern, with 15% of mRNAs enriched in polysomes and exhibiting high expression. Critically, this basal polysomal enrichment had a major impact on FSH-induced mRNA recruitment to the polysomes, since FSH stimulation promoted the release of polysome-enriched mRNAs, while mRNAs that were the least associated to polysomes were preferentially recruited to polysomes upon stimulation. The FSH signal did not alter the core biological functions of Sertoli cells, but shifted the proteins involved in these functions, suggesting a molecular rewiring of the FSH-induced gene expression. These findings underscore how ribosomal reallocation dynamically adapts the cellular translatome to microenvironmental changes, enabling cells to fine-tune protein production in response to external stimuli. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/629416v1_ufig1.gif" ALT="Figure 1000"> View larger version (19K): org.highwire.dtl.DTLVardef@27334forg.highwire.dtl.DTLVardef@199c630org.highwire.dtl.DTLVardef@a28b92org.highwire.dtl.DTLVardef@1794172_HPS_FORMAT_FIGEXP M_FIG C_FIG Bullet points* In Sertoli cells, most mRNAs distribute similarly between monosomes and polysomes, but a sub-population is specifically enriched in polysomes * Basal polysomal enrichment level has a major impact on FSH-induced mRNA recruitment or release from the polysomes * The FSH signal induced a global rewiring of the proteins involved in Sertoli cell basal activity * FSH-induced reassignment of ribosomes to specific mRNAs has to comply with a tightly maintained mRNA distribution landscape

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Leray, X., Morales, J., Trefier, A., Leon, K., Bourquard, T., Musnier, A., Pecnard, E., Drobecq, L., Boulben, S., Azzopardi, N., Coulaud, R., Ouchene, H., Jaszczyszyn, Y., Reiter, E., Guillou, F., Pellissier, L. P., Poupon, A., Yvinec, R., Crepieux, P.. 2024-12-21. Hormone-regulated dynamics of mRNA distribution on ribosomes in Sertoli cells. https://doi.org/10.1101/2024.12.20.629416

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