Numerous Post-translational Modifications of RNA Polymerase II Subunit Rpb4/7 Link Transcription to Post-transcriptional Mechanisms

Richard, Stephen; Gross, Lital; Fischer, Jonathan; Bendalak, Keren; Ziv, Tamar; Urim, Shira; Choder, Mordechai

doi:10.1016/j.celrep.2020.108578

Cited by 19 publications

(22 citation statements)

References 61 publications

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“…The RPB4/RPB7 heterodimer forms a stalk-like protrusion from the Pol II core complex below a mobile clamp domain, adjacent to the CTD of RPB1 and the RNA exit channel, a position with potential for interactions with multiple components such as CTD-bound factors and modifying enzymes and emerging nascent RNAs [ 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. In fact, the RPB4/RPB7 stalk has been proposed to act as an additional landing platform for transcription-related factors, some of which also interact with the CTD [ 38 , 39 ]. It is therefore tempting to speculate that the binding of FluPol to RPB4 synergizes with the CTD-mediated interaction to target nascent capped RNAs.…”

Section: Discussionmentioning

confidence: 99%

The Influenza Virus RNA-Polymerase and the Host RNA-Polymerase II: RPB4 Is Targeted by a PB2 Domain That Is Involved in Viral Transcription

Morel

Sedano

Lejal

et al. 2022

Viruses

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Influenza virus transcription is catalyzed by the viral RNA-polymerase (FluPol) through a cap-snatching activity. The snatching of the cap of cellular mRNA by FluPol is preceded by its binding to the flexible C-terminal domain (CTD) of the RPB1 subunit of RNA-polymerase II (Pol II). To better understand how FluPol brings the 3′-end of the genomic RNAs in close proximity to the host-derived primer, we hypothesized that FluPol may recognize additional Pol II subunits/domains to ensure cap-snatching. Using binary complementation assays between the Pol II and influenza A FluPol subunits and their structural domains, we revealed an interaction between the N-third domain of PB2 and RPB4. This interaction was confirmed by a co-immunoprecipitation assay and was found to occur with the homologous domains of influenza B and C FluPols. The N-half domain of RPB4 was found to be critical in this interaction. Punctual mutants generated at conserved positions between influenza A, B, and C FluPols in the N-third domain of PB2 exhibited strong transcriptional activity defects. These results suggest that FluPol interacts with several domains of Pol II (the CTD to bind Pol II), initiating host transcription and a second transcription on RPB4 to locate FluPol at the proximity of the 5′-end of nascent host mRNA.

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Section: Discussionmentioning

confidence: 99%

The Influenza Virus RNA-Polymerase and the Host RNA-Polymerase II: RPB4 Is Targeted by a PB2 Domain That Is Involved in Viral Transcription

Morel

Sedano

Lejal

et al. 2022

Viruses

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show abstract

“…The RPB4/RPB7 heterodimer forms a stalk-like protrusion from the Pol II core complex below a mobile clamp domain, adjacent to the CTD of RPB1 and the RNA exit channel, a position with potential for interactions with multiple components, such as CTDbound factors and modifying enzymes and emerging nascent RNAs [30][31][32][33][34][35][36]. In fact, the RPB4/RPB7 stalk has been proposed to act as an additional landing platform for transcription-related factors, with some of which known to also interact with the CTD [37,38]. Thus, it is tempting to speculate that the binding of FluPol to RPB4 acts synergistically with its interaction with the CTD to target nascent capped RNAs.…”

Section: Discussionmentioning

confidence: 99%

The Influenza Virus RNA-polymerase and the Host RNA-Polymerase II: RPB4 is Targeted by a PB2 Domain that is Involved in Viral Transcription

Morel¹,

Sedano²,

Lejal³

et al. 2022

Preprint

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Influenza virus transcription is catalyzed by the viral RNA-polymerase (FluPol) through a cap-snatching activity. The snatching of the cap of cellular mRNA by FluPol is preceded by its binding to the flexible C-terminal domain (CTD) of the RPB1 subunit of RNA-polymerase II (Pol II). To better understand how FluPol brings the 3’-end of the genomic RNAs in close proximity to the host-derived primer, we hypothesized that FluPol may recognize additional Pol II subunits/domains to ensure cap-snatching. Using binary complementation assays between the Pol II and FluPol subunits and their structural domains, we revealed an interaction between the N-third domain of PB2 and RPB4. This interaction was confirmed by a co-immunoprecipitation assay and found to occur with the homologous domains of influenza B and C FluPols. Residues [1-72] of RPB4 were found critical in this interaction. Numerous punctual mutants generated at conserved positions between influenza A, B and C FluPols in the N-third domain of PB2 exhibited strong transcriptional activity defect. These results suggest that FluPol interacts with several domains/subunits of Pol II, the CTD to bind Pol II initiating host transcription and a second on RPB4 to locate FluPol at the proximity of the 5’-end of nascent host mRNA.

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“…Several phospho-proteomic studies have identified at least 75 new phospho-sites in 10 of the 12 subunits of S. cerevisiae RNAPII (Supplementary Table S1), 55 of them distributed along specific RNAPII subunits (Rpb1, Rpb2, Rpb3 Rpb4, and Rpb9) and 20 in shared subunits with RNAPI and RNAPIII (Rpb5, Rpb6, Rpb8, Rpb10, and Rpb12) (Albuquerque et al, 2008;Pultz et al, 2012;Swaney et al, 2013;Sostaric et al, 2018;MacGilvray et al, 2020;Lanz et al, 2021;Richard et al, 2021). However, it is unknown whether all these residues are phosphorylated in vivo and if they form part of a regulatory mechanism to control the biogenesis of RNAPII transcripts.…”

Section: Rnapii Phosphorylationmentioning

confidence: 99%

“…Rpb4 and Rpb7 form a heterodimer known as the stalk domain, and only Rpb4 contains phosphorylation sites (Richard et al, 2021). The stalk extends from the foot domain at the base of the RNAPII enzyme and its movement helps to coordinate opening and closing of the clamp (Armache et al, 2003;Bushnell and Kornberg, 2003).…”

Section: Rnapii Phosphorylationmentioning

confidence: 99%

Regulation of Eukaryotic RNAPs Activities by Phosphorylation

González-Jiménez

Campos

Navarro

et al. 2021

Front. Mol. Biosci.

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Evolutionarily conserved kinases and phosphatases regulate RNA polymerase II (RNAPII) transcript synthesis by modifying the phosphorylation status of the carboxyl-terminal domain (CTD) of Rpb1, the largest subunit of RNAPII. Proper levels of Rpb1-CTD phosphorylation are required for RNA co-transcriptional processing and to coordinate transcription with other nuclear processes, such as chromatin remodeling and histone modification. Whether other RNAPII subunits are phosphorylated and influences their role in gene expression is still an unanswered question. Much less is known about RNAPI and RNAPIII phosphorylation, whose subunits do not contain functional CTDs. However, diverse studies have reported that several RNAPI and RNAPIII subunits are susceptible to phosphorylation. Some of these phosphorylation sites are distributed within subunits common to all three RNAPs whereas others are only shared between RNAPI and RNAPIII. This suggests that the activities of all RNAPs might be finely modulated by phosphorylation events and raises the idea of a tight coordination between the three RNAPs. Supporting this view, the transcription by all RNAPs is regulated by signaling pathways that sense different environmental cues to adapt a global RNA transcriptional response. This review focuses on how the phosphorylation of RNAPs might regulate their function and we comment on the regulation by phosphorylation of some key transcription factors in the case of RNAPI and RNAPIII. Finally, we discuss the existence of possible common mechanisms that could coordinate their activities.

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Numerous Post-translational Modifications of RNA Polymerase II Subunit Rpb4/7 Link Transcription to Post-transcriptional Mechanisms

Cited by 19 publications

References 61 publications

The Influenza Virus RNA-Polymerase and the Host RNA-Polymerase II: RPB4 Is Targeted by a PB2 Domain That Is Involved in Viral Transcription

The Influenza Virus RNA-Polymerase and the Host RNA-Polymerase II: RPB4 Is Targeted by a PB2 Domain That Is Involved in Viral Transcription

The Influenza Virus RNA-polymerase and the Host RNA-Polymerase II: RPB4 is Targeted by a PB2 Domain that is Involved in Viral Transcription

Regulation of Eukaryotic RNAPs Activities by Phosphorylation

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