H/ACA snRNP-dependent ribosome biogenesis regulates translation of polyglutamine proteins.

Stem cells in many systems, including Drosophila germline stem cells (GSCs), increase ribosome biogenesis and translation during terminal differentiation. Here, we show that the H/ACA small nuclear ribonucleoprotein (snRNP) complex that promotes pseudouridylation of ribosomal RNA (rRNA) and ribosome biogenesis is required for oocyte specification. Reducing ribosome levels during differentiation decreased the translation of a subset of messenger RNAs that are enriched for CAG trinucleotide repeats and encode polyglutamine-containing proteins, including differentiation factors such as RNA-binding Fox protein 1. Moreover, ribosomes were enriched at CAG repeats within transcripts during oogenesis. Increasing target of rapamycin (TOR) activity to elevate ribosome levels in H/ACA snRNP complex-depleted germlines suppressed the GSC differentiation defects, whereas germlines treated with the TOR inhibitor rapamycin had reduced levels of polyglutamine-containing proteins. Thus, ribosome biogenesis and ribosome levels can control stem cell differentiation via selective translation of CAG repeat-containing transcripts.

Dynamic regulation of ribosome levels and translation during development.

The ability of ribosomes to translate mRNAs into proteins is the basis of all life. While ribosomes are essential for cell viability, reduction in levels of ribosomes can affect cell fate and developmental transitions in a tissue specific manner and can cause a plethora of related diseases called ribosomopathies. How dysregulated ribosomes homeostasis influences cell fate and developmental transitions is not fully understood. Model systems such as Drosophila and C. elegans oogenesis have been used to address these questions since defects in conserved steps in ribosome biogenesis result in stem cell differentiation and developmental defects. In this review, we first explore how ribosome levels affect stem cell differentiation. Second, we describe how ribosomal modifications and incorporation of ribosomal protein paralogs contribute to development. Third, we summarize how cells with perturbed ribosome biogenesis are sensed and eliminated during organismal growth.

Post-transcriptional gene regulation regulates germline stem cell to oocyte transition during Drosophila oogenesis.

During oogenesis, several developmental processes must be traversed to ensure effective completion of gametogenesis including, stem cell maintenance and asymmetric division, differentiation, mitosis and meiosis, and production of maternally contributed mRNAs, making the germline a salient model for understanding how cell fate transitions are mediated. Due to silencing of the genome during meiotic divisions, there is little instructive transcription, barring a few examples, to mediate these critical transitions. In Drosophila, several layers of post-transcriptional regulation ensure that the mRNAs required for these processes are expressed in a timely manner and as needed during germline differentiation. These layers of regulation include alternative splicing, RNA modification, ribosome production, and translational repression. Many of the molecules and pathways involved in these regulatory activities are conserved from Drosophila to humans making the Drosophila germline an elegant model for studying the role of post-transcriptional regulation during stem cell differentiation and meiosis.