A novel evolutionary conserved mechanism of RNA stability regulates synexpression of primordial germ cell-specific genes prior to the sex-determination stage in medaka.

Amaury Herpin,Maëlle Pannetier,Christina Lillesaar,Martina Regensburger,Laurence Ettwiller,Mateus C Adolfi,Aurélie Le Cam,Béatrice Porcon,Yann Guiguen,Dagmar Wilhelm,Manfred Schartl,Brigitte Mourot,Dirk Dolle,Susanne Kneitz,Jérome Montfort,Michael Kraeussling,Clara Gobé,Cornelia Schmidt,Eric Pailhoux

doi:10.1371/journal.pbio.3000185

Abstract

Dmrt1 is a highly conserved transcription factor, which is critically involved in regulation of gonad development of vertebrates. In medaka, a duplicate of dmrt1—acting as master sex-determining gene—has a tightly timely and spatially controlled gonadal expression pattern. In addition to transcriptional regulation, a sequence motif in the 3′ UTR (D3U-box) mediates transcript stability of dmrt1 mRNAs from medaka and other vertebrates. We show here that in medaka, two RNA-binding proteins with antagonizing properties target this D3U-box, promoting either RNA stabilization in germ cells or degradation in the soma. The D3U-box is also conserved in other germ-cell transcripts, making them responsive to the same RNA binding proteins. The evolutionary conservation of the D3U-box motif within dmrt1 genes of metazoans—together with preserved expression patterns of the targeting RNA binding proteins in subsets of germ cells—suggest that this new mechanism for controlling RNA stability is not restricted to fishes but might also apply to other vertebrates.

Highlights

The gonads of vertebrates are characterized by the intimate association of germ cells and supporting somatic cells [1,2,3,4]
The development of the gonads in vertebrates is mainly regulated by dmrt1, a master sexdetermining gene that has a timely and spatially controlled gonadal expression pattern
In addition to transcriptional regulation, a sequence motif located in the 30 UTR (D3U-box) mediates transcript stability of dmrt1 mRNAs

Summary

Introduction

The gonads of vertebrates are characterized by the intimate association of germ cells and supporting somatic cells [1,2,3,4]. The precursor cells of the soma are derived from the embryonic lateral plate mesoderm, whereas germ cells originate from the germline lineage [5,6,7,8,9] To carry out their highly specialized biological functions, the somatic gonadal primordium and the germline cells together must establish timely regulated programs of gene expression [1,10,11]. The mab-3/doublesex/dmrt gene orthologs are, among metazoans, the most evolutionary conserved key regulators of the earliest phases of gonad development They control complex gene regulatory networks specifying male gonadal primordium development as well as gonadal maintenance [12,13,14,15]. Besides being firmly anchored within the regulatory network at critical nodes, dmrt genes were found to act as upstream male sex determiners in organisms as phylogenetically diverse as flatworm [16], water flea [17], frog [18], flatfish [19], birds [20] and medaka [21,22]

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Discussion

Conclusion