Transcription Elongation by RNA Polymerase I Is Linked to Efficient rRNA Processing and Ribosome Assembly

Schneider, David A.; Michel, Antje; Sikes, Martha L.; Vu, Loan; Dodd, Jonathan A.; Salgia, Shilpa R.; Osheim, Yvonne N.; Beyer, Ann L.; Nomura, Masayasu

doi:10.1016/j.molcel.2007.04.007

Cited by 121 publications

(137 citation statements)

References 56 publications

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“…By using qChIP analysis to evaluate Pol I loading onto the rDNA in combination with pulse metabolic labelling to measure newly synthesized 47S pre-rRNA, we demonstrated that acute serum withdrawal from exponentially growing cells inhibited 47S prerRNA synthesis without changing Pol I loading onto the rDNA. This suggests that growth factor signalling is required for transcription elongation and possibly cotranscriptional processing of rRNA, which is known to be coupled to elongation in yeast [36,50]. Consistent with this finding, enhanced transcription initiation mediated by Rrn3 overexpression was not sufficient to promote full length 47S pre-rRNA synthesis under serum starvation conditions, despite elevated Pol I loading at the rDNA.…”

Section: Accepted Manuscript 18mentioning

confidence: 65%

“…Emerging evidence however, suggests that the elongation step in Pol I transcription is important for the overall control of rRNA synthesis rate as well as ensuring efficient rRNA processing [33][34][35][36][37]. In contrast to the model of initiation regulation,…”

Section: Accepted Manuscriptmentioning

confidence: 95%

“…These findings clearly demonstrate the essential role of post-initiation steps in the regulation of rRNA synthesis by growth factors. Certainly, work in yeast revealed a complex interplay between rRNA production, assembly, cleavage, and folding that occurs during elongation [36,51]. Uncovering how elongation is regulated and how it is coupled to rRNA assembly will lead to major advances towards understanding the mechanisms of rRNA production [49].…”

Section: Accepted Manuscript 18mentioning

confidence: 99%

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Cell cycle and growth stimuli regulate different steps of RNA polymerase I transcription

Hung

Lesmana

Peck

et al. 2017

Gene

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, Cell cycle and growth stimuli regulate different steps of RNA polymerase I transcription. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Gene(2016Gene( ), doi: 10.1016Gene( /j.gene.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T A C C E P T E D M A N U S C R I P T 3 AbstractTranscription of the ribosomal RNA genes (rDNA) by RNA Polymerase I (Pol I) is a major control step for ribosome synthesis and is tightly linked to cellular growth.However, the question of whether this process is modulated primarily at the level of transcription initiation or elongation is controversial. Studies in markedly different cell types have identified either initiation or elongation as the major control point. In this study, we have re-examined this question in NIH3T3 fibroblasts using a combination of metabolic labelling of the 47S rRNA, chromatin immunoprecipitation analysis of Pol I and overexpression of the transcription initiation factor Rrn3. Acute manipulation of growth factor levels altered rRNA synthesis rates over 8-fold without changing Pol I loading onto the rDNA. In fact, robust changes in Pol I loading were only observed under conditions where inhibition of rDNA transcription was associated with chronic serum starvation or cell cycle arrest. Overexpression of the transcription initiation factor Rrn3 increased loading of Pol I on the rDNA but failed to enhance rRNA synthesis in either serum starved, serum treated or G0/G1 arrested cells. Together these data suggest that transcription elongation is rate limiting for rRNA synthesis. We propose that transcription initiation is required for rDNA transcription in response to cell cycle cues, whereas elongation controls the dynamic range of rRNA synthesis output in response to acute growth factor modulation.

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Section: Accepted Manuscript 18mentioning

confidence: 65%

Section: Accepted Manuscriptmentioning

confidence: 95%

Section: Accepted Manuscript 18mentioning

confidence: 99%

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Cell cycle and growth stimuli regulate different steps of RNA polymerase I transcription

Hung

Lesmana

Peck

et al. 2017

Gene

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“…MTERF3 and mtRNA polymerase were both identified as interacting with RNMTL1, possibly mediated by RNA structures (Table 1). Elegant experiments have shown that the rate of transcription by nuclear RNA polymerase I is coupled to events in rRNA modification and ribosome assembly (56). MTERF3 and the complex of MTERF4-NSUN4 may operate in a similar manner in mitochondria (19).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Ribosomal RNA (rRNA) Methyltransferase Family Members Are Positioned to Modify Nascent rRNA in Foci near the Mitochondrial DNA Nucleoid

Lee

Okot-Kotber²,

LaComb

et al. 2013

Journal of Biological Chemistry

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Background: Mitochondrial rRNAs contain site-specific modifications, including methylated residues, but few of the enzymes responsible for these modifications have been found. Results: RNMTL1, MRM1, and MRM2 are methyltransferase family members found associated with the mtDNA nucleoid and with the large ribosomal subunit. Conclusion:The association of putative RNA-modifying enzymes with nucleoids and ribosomes supports the model that assembly of mitochondrial ribosomes begins while rRNA transcription continues. Significance: This work advances understanding of the assembly of mitochondrial ribosomes necessary for biosynthesis of the respiratory chain.

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“…It is proposed that the production of ribosomes depends on a kinetic balance between the rate of rRNA synthesis and the rates of rRNA folding and maturation. 44 DFC is generated by elongation of rDNA transcription and the first cleavage-modification steps of pre-rRNAs. Late cleavage-processing steps and assembly of the large ribosome subunits generate the GC.…”

Section: Discussionmentioning

confidence: 99%

The traffic of proteins between nucleolar organizer regions and prenucleolar bodies governs the assembly of the nucleolus at exit of mitosis

Muro¹,

Gébrane-Younès²,

Jobart-Malfait³

et al. 2010

Nucleus

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is also a plurifunctional domain involved in assembly of RNPs and a target for viral proteins and viral RNAs. [8][9][10][11] The assembly of the nucleolus starts during telophase by activation of rDNA transcription of several nucleolar organizer regions (NORs) and by progressive recruitment of early and late processing proteins on rRNA transcripts. In parallel, prenucleolar bodies (PNBs) are assembled. [12][13][14][15][16] The PNBs contain nucleolar processing proteins, pre-rRNAs and snoRNAs. 17 Even though PNBs are formed in all animal and plant cells, their role in the dynamics of DFC and GC assembly is still unknown.It is possible to observe and measure the motion of proteins or RNP complexes in living cells. Using these approaches it was demonstrated that macromolecules within the nucleus are highly mobile by a combination of passive diffusion and highaffinity binding sites. [18][19][20] It was also established that the assembly of nuclear bodies after mitosis is strictly ordered. 14,[21][22][23][24] It is now important to characterize the dynamics of the complexes during the building of the functional domains integrated in the nuclear network. We examined the role of the PNB step in the kinetics of DFC and GC assembly. Using photoactivation, 25 weThe building of nuclear bodies after mitosis is a coordinated event crucial for nuclear organization and function. The nucleolus is assembled during early G 1 phase. Here, two periods (early G1a and early G1b) have been defined. During these periods, the nucleolar compartments (DFC, GC) corresponding to different steps of ribosome biogenesis are progressively assembled. In telophase, rDNA transcription is first activated and PNBs (reservoirs of nucleolar processing proteins) are formed. The traffic of the processing proteins between incipient nucleoli and PNBs was analyzed using photoactivation. We demonstrate that the DFC protein fibrillarin passes from one incipient nucleolus to other nucleoli but not to PNBs, and that the GC proteins, B23/NPM and Nop52, shuttle between PNBs and incipient nucleoli. This difference in traffic suggests a way of regulating assembly first of DFC and then of GC. The time of residency of GC proteins is high in incipient nucleoli compared to interphase nuclei, it decreases in LMB-treated early G1a cells impairing the assembly of GC. Because the assembly of the nucleolus and that of the Cajal body at the exit from mitosis are both sensitive to CRM1 activity, we discuss the fact that assembly of GC and/or its interaction with DFC in early G1a depends on shuttling between PNBs and NORs in a manner dependent on Cajal body assembly.www.landesbioscience.comNucleus 203 RESEARCH PAPER decreases as expected of proteins trafficking between nucleolus and nucleoplasm. Surprisingly, activated PAGFP-B23/NPM is detected in PNBs 5-10 seconds after activation (Fig. 1D). The uptake of B23/NPM in PNBs is observed in all PNBs containing mDsRed-Nop52 visible in the focal plane. This indicates that feedback of activated molecules occurs between incipient nuc...

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Transcription Elongation by RNA Polymerase I Is Linked to Efficient rRNA Processing and Ribosome Assembly

Cited by 121 publications

References 56 publications

Cell cycle and growth stimuli regulate different steps of RNA polymerase I transcription

Cell cycle and growth stimuli regulate different steps of RNA polymerase I transcription

Mitochondrial Ribosomal RNA (rRNA) Methyltransferase Family Members Are Positioned to Modify Nascent rRNA in Foci near the Mitochondrial DNA Nucleoid

The traffic of proteins between nucleolar organizer regions and prenucleolar bodies governs the assembly of the nucleolus at exit of mitosis

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