Review Reports

Round 1

Reviewer 1 Report

The MS by Sadurnì and Saponaro is a comprehensive overview about the involvement of RNA polymerase II in human tumours. The paper is clearly written and I have only minor suggestions to improve the MS.

 

1.  Introduction section, page 2 lines 46-51. In this paragraph an important information is lacking. TFs, either activators or repressors, do not work alone but with co-activators (-repressors) fundamental for RNAPs loading onto chromatin (or detachment). Please, include this information with the related mechanisms of chromatin decondensation/condensation and appropriate references.

 

2. For the MS consistency, add a description on the subunit composition of RNAPI and III at the beginning of the related paragraph describing their alteration in cancer.

 

3. The reference Luo et., al 2009, cited at line 239 is missing. Line 239: reference Huang & Vakoc, 2016 is a comment on the work of Iorio et al., on Cell, 2016. This is the correct reference to cite. I suggest to control that all the references cited in the MS have been reported.

Author Response

The MS by Sadurnì and Saponaro is a comprehensive overview about the involvement of RNA polymerase II in human tumours. The paper is clearly written and I have only minor suggestions to improve the MS.

We welcome the positive feedback from the reviewer and are happy to incorporate their suggestions in our manuscript.

1. Introduction section, page 2 lines 46-51. In this paragraph an important information is lacking. TFs, either activators or repressors, do not work alone but with co-activators (-repressors) fundamental for RNAPs loading onto chromatin (or detachment). Please, include this information with the related mechanisms of chromatin decondensation/condensation and appropriate references.

We agree with the recommendation of the reviewer and have also included for completeness a small section in the introduction to mention the roles of coactivators and corepressors, and the general mechanisms through which they can regulate and/or strengthen the activities of TFs.

2. For the MS consistency, add a description on the subunit composition of RNAPI and III at the beginning of the related paragraph describing their alteration in cancer.

We agree that being this a review that summarises what is known about single RNA Polymerases subunits deregulations, some more information about RNA Pol I and III would be needed. We have now included in the paragraphs about RNA Pol I and III additional information about the deregulation of their single subunits. These sections are not as extensive as in the case of Pol II subunits, as limited information is available in the literature.

3. The reference Luo et., al 2009, cited at line 239 is missing. Line 239: reference Huang & Vakoc, 2016 is a comment on the work of Iorio et al., on Cell, 2016. This is the correct reference to cite. I suggest to control that all the references cited in the MS have been reported.

We apologise for this mistake and have checked the correctness of all references.

Reviewer 2 Report

In their review “Deregulations of RNA Pol II subunits in cancer”, Sadurni and Saponaro review an interesting aspects related to potential role of deregulated levels of RNA pol II subunits in cancer.  The review covers an important aspects of the field that have not been previously reviewed. It is well structured, well written and informative. The figures are nice and easy to follow. 

Specific suggestions:

The review nicely summarises literature related to specific alterations in Pol II subunits found in different cancers. What is missing in my opinion is discussion of how could the reported alterations impact transcription. Authors should discuss roles of individual subunits and how they contribute to transcription and link this to what might happen when levels of subunits are dysregulated. Perhaps interaction with the transcription factors can be affected, Pol II stoichiometry and recycling?  

Author Response

In their review “Deregulations of RNA Pol II subunits in cancer”, Sadurni and Saponaro review an interesting aspects related to potential role of deregulated levels of RNA pol II subunits in cancer.  The review covers an important aspects of the field that have not been previously reviewed. It is well structured, well written and informative. The figures are nice and easy to follow. 

Specific suggestions:

The review nicely summarises literature related to specific alterations in Pol II subunits found in different cancers. What is missing in my opinion is discussion of how could the reported alterations impact transcription. Authors should discuss roles of individual subunits and how they contribute to transcription and link this to what might happen when levels of subunits are dysregulated. Perhaps interaction with the transcription factors can be affected, Pol II stoichiometry and recycling?  

We are pleased with the reviewer’s comment and the overall positive feedback about our manuscript. The discussion section has been greatly expanded highlighting how during the transcription process the RNA Pol II complex interacts with a series of transcription factors, and highlighting those cases where we know of specific subunits being important for the interaction between the RNA Pol II complex and TFs. Moreover, we have also included how deregulation of RNA Pol II subunits may have an impact on the deregulation of also Pol I and Pol III transcription.

 

Round 2

Reviewer 1 Report

Dear Authors, thank you for having fulfilled my requests. My recommendation will be "Accept". With my best wished for your future work.