Differential regulation of RNA polymerase III genes during liver regeneration

Yeganeh, Meghdad; Praz, Viviane; Carmeli, Cristian; Villeneuve, Dominic; Rib, Leonor; Guex, Nicolas; Herr, Winship; Delorenzi, Mauro; Hernandez, Nouria

doi:10.1093/nar/gky1282

Cited by 15 publications

(19 citation statements)

References 35 publications

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“…We found that pol III occupancy in the liver of WT mice decreases during the fed to fasted transition but this response is limited to mostly low and intermediate occupancy genes; high occupancy genes are essentially unchanged. Similar findings involving overlapping subsets of stable and changing genes are seen following a partial hepatectomy 18 . In contrast, in Maf1 -/mice, pol III occupancy was increased for the majority of active loci in liver, regardless of their occupancy level, and the levels of specific precursor tRNAs in this tissue and in other organs are higher than wild-type in both fed and fasted conditions.…”

Section: Introductionsupporting

confidence: 62%

“…(i) Of the 212 high occupancy genes in the PH dataset (average occupancy score > 3.5, see Table S4 in ref 18 ), 197 were not significantly changed by PH. Of these, 90% (177 genes) were also not significantly changed upon fasting ( Figure 1C, black dots).…”

Section: Fasting and Refeeding Affects Pol III Occupancy In Mouse Livermentioning

confidence: 99%

“…(C) Color mapping of pol III occupancy relationships between nutritional and proliferative signaling responses. The fasting/refeeding data in panel B are colored based on the fold change in occupancy scores before and 36 hours after partial hepatectomy (PH) 18 . Black dots, no occupancy change upon feeding/fasting or PH; green dots, reciprocal changes in pol III occupancy upon feeding/fasting and PH; red dots, genes with higher sensitivity to PH than to feeding; blue and magenta dots, genes with higher sensitivity to feeding than to PH.…”

Section: Data Availabilitymentioning

confidence: 99%

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MAF1 is a Chronic Repressor of RNA Polymerase III Transcription in the Mouse

Bonhoure

Praz

Moir

et al. 2019

Preprint

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Maf1 -/mice are lean, obesity-resistant and metabolically inefficient. Their increased energy expenditure is thought to be driven by a futile RNA cycle that reprograms metabolism to meet an increased demand for nucleotides stemming from the deregulation of RNA polymerase (pol) III transcription. Metabolic changes consistent with this model have been reported in both fed and fasted mice, however the impact of the feeding-fasting cycle on pol III function has not been examined. Here we show that changes in pol III occupancy in the liver of fed versus fasted wild-type mice are largely confined to low and intermediate occupancy genes; high occupancy genes are unchanged. However, in Maf1 -/mice, pol III occupancy of the vast majority of active loci in liver and the levels of specific precursor tRNAs in this tissue and other organs are higher than wild-type in both fed and fasted conditions. Thus, MAF1 functions as a chronic repressor of active pol III loci and can modulate transcription under different conditions. Our findings support the futile RNA cycle hypothesis, elaborate the mechanism of pol III repression by MAF1 and demonstrate a modest effect of MAF1 on global translation via reduced mRNA levels and translation efficiencies for several ribosomal proteins. Affiliations

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Section: Introductionsupporting

confidence: 62%

Section: Fasting and Refeeding Affects Pol III Occupancy In Mouse Livermentioning

confidence: 99%

Section: Data Availabilitymentioning

confidence: 99%

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MAF1 is a Chronic Repressor of RNA Polymerase III Transcription in the Mouse

Bonhoure

Praz

Moir

et al. 2019

Preprint

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“…Pol III transcription is regulated in different biological processes such as the cell cycle (White et al 1995), differentiation (Alla and Cairns 2014;Van Bortle et al 2017), development (Schmitt et al 2014), regeneration (Yeganeh et al 2019), and cellular stress (Upadhya et al 2002). Its activity is controlled by MAF1, a protein conserved from yeast to human that binds to the enzyme and represses its activity, and by a number of tumor suppressors and oncogene products that act on Pol III transcription factors (for review, see Marshall and White 2008;Gjidoda and Henry 2013).…”

mentioning

confidence: 99%

RNA polymerase III transcription as a disease factor

Yeganeh

Hernandez

2020

Genes Dev.

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RNA polymerase (Pol) III is responsible for transcription of different noncoding genes in eukaryotic cells, whose RNA products have well-defined functions in translation and other biological processes for some, and functions that remain to be defined for others. For all of them, however, new functions are being described. For example, Pol III products have been reported to regulate certain proteins such as protein kinase R (PKR) by direct association, to constitute the source of very short RNAs with regulatory roles in gene expression, or to control microRNA levels by sequestration. Consistent with these many functions, deregulation of Pol III transcribed genes is associated with a large variety of human disorders. Here we review different human diseases that have been linked to defects in the Pol III transcription apparatus or to Pol III products imbalance and discuss the possible underlying mechanisms.

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“…However, based on differential binding of RNAPIII, many studies have revealed that tRNA genes are not equally transcribed in mammalian cells, as measured by the differential binding of RNAPIII (7-9). Genome-wide studies examining chromatin accessibility, modification and transcription factor binding have suggested that a driver of RNAPIII occupancy at tRNA genes is open and active chromatin, typically in the vicinity of RNAPII transcription sites, yet the basis for differential RNAPIII binding remains to be determined (7,8,49,50). Further studies are needed to assess how host chromatin accessibility and modifications change during MHV68 infection.…”

Section: Discussionmentioning

confidence: 99%

Alteration of the premature tRNA landscape by gammaherpesvirus infection

Tucker

Schaller

Willis

et al. 2019

Preprint

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12Transfer RNAs (tRNAs) are transcribed by RNA polymerase III (RNAPIII) and play a 13 central role in decoding our genome. Many DNA tumor viruses enhance the activity of RNAPIII, 14 yet whether infection alters tRNA expression is largely unknown. Here, we present the first 15 genome wide analysis of how viral infection alters the tRNAome. Using a tRNA-specific 16 sequencing method (DM-tRNA-seq), we find that the murine gammaherpesvirus MHV68 17 induces global changes in pre-tRNA expression, indicating that differential tRNA gene induction 18 is a characteristic of DNA virus infection. Elevated pre-tRNA expression corresponds to 19 increased RNAPIII occupancy, but post-transcriptional mechanisms also contribute. Pre-tRNA 20 accumulation, but not RNAPIII recruitment, requires the virally encoded mRNA endonuclease 21 muSOX, suggesting interplay between the different facets of virus-induced gene regulation. 22Collectively, these findings reveal pervasive changes to tRNA expression during DNA virus 23 infection and highlight the potential of using viruses to explore tRNA biology. 24 25 Impact 26 The first genome-wide analysis of virus-induced tRNA expression changes reveals that 27 tRNA transcription and processing are perturbed by the gammaherpesvirus MHV68. 28 29 30The elegant design of the tRNA decoder, an adaptor molecule which converts genetic 31 information into protein, was proposed over 60 years ago (1). Although tRNAs were the first 32 non-coding RNA described, our understanding of tRNA biology, especially their functions 33 outside of protein translation and what dictates their expression, remains limited. This is partly 34 due to the difficulties in applying RNA sequencing and analysis platforms to tRNAs, but recent 35 methodological advances have resulted in a surge of new studies that help to resolve these 36 complexities (2-4). Non-canonical functions of tRNA transcripts have been described, namely 37 the discovery that both premature and mature tRNAs undergo fragmentation into shorter RNAs 38 with numerous regulatory functions in response to stress, cancer, and viral infection (reviewed 39 in (5, 6)). Given the evidence that the ~400 predicted tRNA genes in mammalian genomes are 40 differentially expressed across cell lines (7-9) and that viral infection can lead to post-41 transcriptional modulation of tRNAs (10, 11), defining the tRNAome under varying conditions will 42 be central to our understanding of tRNA function, canonical and otherwise. 43RNA polymerase III (RNAPIII) transcribes tRNA genes and exhibits enhanced activity 44 during infection with DNA viruses (12-17), many of which encode their own RNAPIII genes. 45Though RNAPIII activation stimulates expression of viral RNAPIII genes, concomitant 46 accumulation of host RNAPIII transcripts can trigger antiviral immune responses. For example, 47 the induction or misprocessing of RNAPIII-generated host 5S RNA pseudogene and vault RNA 48 transcripts during Herpes Simplex Virus-1 (HSV-1) and Kaposi's sarcoma-associated 49 herpesvirus (KSHV) infection...

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Differential regulation of RNA polymerase III genes during liver regeneration

Cited by 15 publications

References 35 publications

MAF1 is a Chronic Repressor of RNA Polymerase III Transcription in the Mouse

MAF1 is a Chronic Repressor of RNA Polymerase III Transcription in the Mouse

RNA polymerase III transcription as a disease factor

Alteration of the premature tRNA landscape by gammaherpesvirus infection

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