Maternal Nanos inhibits Importin-α2/Pendulin-dependent nuclear import to prevent somatic gene expression in the Drosophila germline

Abstract

Repression of somatic gene expression in germline progenitors is one of the critical mechanisms involved in establishing the germ/soma dichotomy. In Drosophila , the maternal Nanos (Nos) and Polar granule component (Pgc) proteins are required for repression of somatic gene expression in the primordial germ cells, or pole cells. Pgc suppresses RNA polymerase II-dependent global transcription in pole cells, but it remains unclear how Nos represses somatic gene expression. Here, we show that Nos represses somatic gene expression by inhibiting translation of maternal importin-α2 ( impα2 ) mRNA. Mis-expression of Impα2 caused aberrant nuclear import of a transcriptional activator, Ftz-F1, which in turn activated a somatic gene, fushi tarazu ( ftz ), in pole cells when Pgc-dependent transcriptional repression was impaired. Because ftz expression was not fully activated in pole cells in the absence of either Nos or Pgc, we propose that Nos-dependent repression of nuclear import of transcriptional activator(s) and Pgc-dependent suppression of global transcription act as a ‘double-lock’ mechanism to inhibit somatic gene expression in germline progenitors.

Spatiotemporal gating of Stat nuclear influx by Drosophila Npas4 in collective cell migration

“…UAS- upd ( 83 ) and UAS- hop ( 84 ) were obtained from Yu-Chen Tsai. UAS- pen (UASp- imp α 2-3xMyc ) was a gift from S. Kobayashi ( 85 ). hsFLP ; FRT82B , ubi-rfp was a gift from Chi Kuang Yao.…”

Antagonism between germ cell-less and Torso receptor regulates transcriptional quiescence underlying germline/soma distinction

“…Nos is a translation factor and thus must block transcription indirectly. Together with the RNA-binding protein Pumilio (Pum), Nos interacts with recognition sequences in the 3’-untranslated regions (3’UTRs) of mRNAs and inhibits their translation ( Asaoka et al, 2019 ; Sonoda and Wharton, 1999 ; Wharton and Struhl, 1991 ). Currently, the key mRNA target(s) that Nos-Pum repress to block transcription is unknown; however, in nos and pum mutants, PGC nuclei display high levels of Ser5 and Ser2 CTD phosphorylation and activate transcription of gap and pair-rule patterning genes and the sex determination gene Sex-lethal ( Sxl ) ( Deshpande et al, 2005 ; Deshpande et al, 1999 ).…”

Trajectory Mapping of the Early Drosophila Germline Reveals Controls of Zygotic Activation and Sex Differentiation

“…For genes that encode RNA-binding proteins, there are three that are germline-specific and expressed prior to zygotic activation: nos, oskar, and bru1. Notably, they all have known functions in regulating early germline development (Asaoka et al, 2019;Kim-Ha et al, 1995;Lehmann and Nüsslein-Volhard, 1986). Moreover, there is an example of nos regulating stability of a transcript in the embryonic germline (Sugimori et al 2018).…”

“…In D. melanogaster, germ plasm loaded in the posterior of oocytes contains RNAs and proteins that are important for germline specification and early germline characteristics such as repression of transcription and migration (Santos and Lehmann, 2004). The phase of transcriptional quiescence is thought to prevent erratic expression of somatic genes (Hanyu-Nakamura et al 2008;Asaoka et al 2019). However, we do not have a clear understanding of what occurs downstream of specification that embodies the germline program which actively drives the specific development of this lineage.…”