Abstract
ABSTRACTPWP1 is a chromatin binding protein with an important role in animal growth control downstream of mTOR-mediated nutrient sensing. PWP1 has been shown to control tissue growth by promoting the transcription of 5.8S, 18S and 28S ribosomal RNAs (rRNAs) by RNA polymerase I (Pol I). Concomitantly with Pol I, RNA Polymerase III (Pol III) contributes to ribosome biogenesis by transcribing 5S rRNA in the nucleoplasm. Pol III activity is also closely controlled by nutrient-dependent signaling, however, how the activities of Pol I and Pol III are coordinated in response to nutrient-derived signals remains insufficiently understood. Experiments in Drosophila larvae and human cells reported here show that PWP1 associates with the chromatin at the 5S rDNA loci and is needed for nutrient-induced expression of 5S rRNA. Similar to the Pol I target rDNAs, PWP1 epigenetically maintains 5S rDNA in a transcription competent state. Thus, as a common regulator of Pol I and Pol III, PWP1 might contribute to coordinated control of ribosomal gene expression in response to nutrition.This article has an associated First Person interview with the first author of the paper.
Highlights
Animal growth is dynamically regulated in response to environmental factors, including nutrients
Our previous study showed that PWP1 acts downstream of nutrientresponsive mTOR signaling in vivo in Drosophila and that PWP1 is essential for the induced expression of the polymerase I (Pol I)-dependent ribosomal RNAs (rRNAs) in response to protein-rich diet (Liu et al, 2017)
As the Pol IIIdependent gene expression is dependent on nutrition (Marshall et al, 2012), we wanted to test if Drosophila PWP1 controls the expression of Pol IIIdependent 5S rRNA in this setting
Summary
Animal growth is dynamically regulated in response to environmental factors, including nutrients. Ribosome biogenesis serves as a limiting factor for growth capacity and it is tightly controlled by nutrient-responsive signaling, including the mTOR (mechanistic target of rapamycin) pathway (Saxton and Sabatini, 2017). The ribosomal RNAs (rRNAs) are transcribed by RNA polymerases (Pols) I and III (Koš and Tollervey, 2010; Moir and Willis, 2013). MTOR signaling promotes the activities of both Pol I and III in response to nutrition, but the known downstream effectors are distinct. Received 20 August 2018; Accepted 3 October 2018 activate Pol I, while in the case of Pol III regulation, mTOR phosphorylates and inhibits the repressor Maf (Mayer and Grummt, 2006; Rideout et al, 2012)
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