Transcriptional control of ribosome biogenesis in yeast: links to growth and stress signals

Abstract

Ribosome biogenesis requires prodigious transcriptional output in rapidly growing yeast cells and is highly regulated in response to both growth and stress signals. This minireview focuses on recent developments in our understanding of this regulatory process, with an emphasis on the 138 ribosomal protein genes (RPGs) themselves and a group of >200 ribosome biogenesis (RiBi) genes whose products contribute to assembly but are not part of the ribosome. Expression of most RPGs depends upon Rap1, a pioneer transcription factor (TF) required for the binding of a pair of RPG-specific TFs called Fhl1 and Ifh1. RPG expression is correlated with Ifh1 promoter binding, whereas Rap1 and Fhl1 remain promoter-associated upon stress-induced down regulation. A TF called Sfp1 has also been implicated in RPG regulation, though recent work reveals that its primary function is in activation of RiBi and other growth-related genes. Sfp1 plays an important regulatory role at a small number of RPGs where Rap1–Fhl1–Ifh1 action is subsidiary or non-existent. In addition, nearly half of all RPGs are bound by Hmo1, which either stabilizes or re-configures Fhl1–Ifh1 binding. Recent studies identified the proline rotamase Fpr1, known primarily for its role in rapamycin-mediated inhibition of the TORC1 kinase, as an additional TF at RPG promoters. Fpr1 also affects Fhl1–Ifh1 binding, either independently or in cooperation with Hmo1. Finally, a major recent development was the discovery of a protein homeostasis mechanism driven by unassembled ribosomal proteins, referred to as the Ribosome Assembly Stress Response (RASTR), that controls RPG transcription through the reversible condensation of Ifh1.

Dedicated chaperones coordinate co-translational regulation of ribosomal protein production with ribosome assembly to preserve proteostasis

“…As mentioned in the Introduction, the complementary action of Ifh1 and Sfp1, which are predominantly required for activation of either category I and II (Ifh1) or category III (Sfp1) RPG promoters, ensures the co-regulated expression of all RPGs under most conditions ( Zencir et al, 2020 ; Shore et al, 2021 ). Ifh1, owing to its Utp22-dependent sequestration in the CURI complex, is also employed, by sensing the 90S assembly status, to coordinate the transcriptional output of most RPGs with that of the 35S pre-rRNA ( Albert et al, 2016 ).…”

“…As a first mechanism to ensure the roughly equimolar supply of each r-protein, RPG transcription is regulated such that the output for each of the 79 RPG mRNAs, regardless of whether derived from a single-copy or duplicated RPG, is within a similar range ( Zeevi et al, 2011 ; Knight et al, 2014 ). This co-regulation of the three different RPG promoter types is mediated by the complementary action of the two TORC1-controlled transcription factors Ifh1 and Sfp1, which are either mainly required for activation of category I and II (Ifh1) or category III (Sfp1) promoters ( Zencir et al, 2020 ; Shore et al, 2021 ). Moreover, RPG transcription is also coordinated with RNA Pol I activity via Utp22-dependent sequestration of Ifh1 in the CURI complex ( Albert et al, 2016 ).…”

Response to Cold: A Comparative Transcriptomic Analysis in Eight Cold-Adapted Yeasts

“…A considerable number of genes for ribosomal subunits were upregulated in P. glacialis and Tetracladium sp. Based on these findings and that proteosomes are complex and involved in proteolytic pathways, including normal and damaged proteins ( Goldberg, 2003 ; Wang et al, 2010 ) and ribosome biogenesis is considered one of the most energy-demanding cellular processes ( Shore et al, 2021 ), clearly C. sake and W. anomalus were the yeasts most affected by the temperature switch to 4°C. Therefore, we could speculate that their response is rather slow down cellular processes and prepare to enter dormancy.…”

Dedicated chaperones coordinate co-translational regulation of ribosomal protein production with ribosome assembly to preserve proteostasis

“…As mentioned in the Introduction, the complementary action of Ifh1 and Sfp1, even though being predominantly required for activation of either category I and II (Ifh1) or category III (Sfp1) RPG promoters, ensures the co-regulated expression of all RPGs under most conditions (Zencir et al ., 2020; Shore et al ., 2021). Ifh1, owing to its Utp22-dependent sequestration in the CURI complex, is also employed, by sensing the 90S assembly status, to coordinate the transcriptional output of most RPGs with that of the 35S pre-rRNA (Albert et al ., 2016).…”