Small RNAs Worm Up Transgenerational Epigenetics Research
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe review by Dr. Grishok is an interesting survey of findings that pertain to epigenetic research in C. elegans, although in the end it is really mostly focused on transgenerational epigenetic phenomena and the role of small RNAs in this process.
Overall the review was quite interesting as it discussed some of the newest
developments that were presented at the recent International C. elegans Conference which was held remotely this year due to the current pandemic. It was well written for the most part with the exception of a few typos and grammatical issues which I have listed at the end of these paragraphs.
The scope of the work that is covered in the review does not accurately reflect the title that Dr. Grishok has chosen. Perhaps I would recommend that the author think of expanding their topic to include some significant findings that would likely be of additional interest to investigators that are interested in epigenetic mechanisms and their implications. Ideas that might be interesting to add might include the discovery of m6A and its potential affects on gene expression, description of some of the mortal germ line phenotypes described in animals with prg-1 mutations, changes in H3K4me2 methylation/demethylation, or following starvation in mutants that lack AMPK, might broaden the scope of the review somewhat, beyond a small RNA focused topic, thus making it a bit more general. Alternatively, perhaps the title could be changed to indicate that the review is focused on small RNA based mechanisms in transgenerational epigenetic inheritance.
The writing bounces back and forth between older findings and those that are quite recent or still preliminary. A more balanced progression through the various topics building on what was known to what we are now finding out might be more effective, or pointing out the major questions in the field and adding new developments in our attempts to answer them. Neither of these are major problems with the review, but careful thought about making it flow a bit better might improve it further.
The conclusion section is very disappointing. After introducing the reader to all these new exciting findings I am sure Dr. Grishok can elaborate a bit further on some of the potential implications and where things might be heading in the future.
Minor issues:
The following is a list of grammatical issues and/or typos that need to be modified by the author to improve the quality of the writing and the ability convey the correct information to the reader. The list may not be comprehensive so I urge the author to have the work re-read by a colleague.
Germline is used incorrectly throughout."Germ line" is a noun; "germline" is an adjective
Line 7- insert "the"; is central to the propagation and evolution
Line 13- remove the; in the epigenetic research
Line 34-replace has been with was; has been discovered
Line 36-gene names should be italicized throughout; lin-4 – in 1993 [2,3], and let-7 – in 2000
Line 38- remove in; RNA drugs in beyond
Line 39- replace were not yet with "not been"; had miRNAs were not yet discovered.
Line 42-insertal environmental challenges; adaptive responses to environment
Line 45 - insert "a" after interest; interest wide
Line 51- insert "The" at the beginning of the sentence; First indication
LIne 84 - gave rise to monitoring germline... might read better as "this allowed investigators to monitor germline..."
Line 101- For a long time, the dependence...might read better as "until very recently, the dependence..."
Line 107-insert "the"; in the F1 generation
Line 113- replace separated by "bound"; not separated by membranes,
Line 113- End sentence after germ line. These granules contain; C. elegans germline; they contain
Line 115- replace were detected with "are present"P-granules, were detected in oocytes
Line 122- I think it would be interesting to include how these granules have recently been found to fall into different categories with distinct roles in both small RNA mediated processes that include, but are not exclusive to TEI.
Line 123-insert "forms of" after limited; limited forms of TEI
Line 125- insert "the epigenetic mechanisms involved in" after of; understanding of the epigenetic mechanisms involved in endogenous
Line 135- insert "r"; undescoring
Line 139-replace the with "a"; display the mortal germline
Line 140-replace "in" with "over multiple"; increases in generations
Line 144-replace mortal germline with "the Mrt phenotype"
Lines 150-154 do not convey the message very effectively. This section is awkward and could be re-written
Line 162- add "the" and insert space in germ line; in the germ lines of all animals [62].
Line 171- insert "successive"; persisted in successive generations
Line 180-the propagation of adaptation in generations might read better as "propagation of the adaptive response(s) through generations."
Line 241-remove "The" in The CENP...
Line 244-"holocentric: in this case," might read better as "holocentric, so CENP-A...
Line 248-should be not clear; still nor clear
Lines 248, 249- de-novo should be de novo
Author Response
Response to Reviewer 1 Comments
Point 1: The scope of the work that is covered in the review does not accurately reflect the title that Dr. Grishok has chosen. Perhaps I would recommend that the author think of expanding their topic to include some significant findings that would likely be of additional interest to investigators that are interested in epigenetic mechanisms and their implications. Ideas that might be interesting to add might include the discovery of m6A and its potential effects on gene expression, description of some of the mortal germ line phenotypes described in animals with prg-1 mutations, changes in H3K4me2 methylation/demethylation, or following starvation in mutants that lack AMPK, might broaden the scope of the review somewhat, beyond a small RNA focused topic, thus making it a bit more general. Alternatively, perhaps the title could be changed to indicate that the review is focused on small RNA based mechanisms in transgenerational epigenetic inheritance.
Response 1: The title of the manuscript has been revised to “Small RNAs Worm up Transgenerational Epigenetics Research”
Point 2: The writing bounces back and forth between older findings and those that are quite recent or still preliminary. A more balanced progression through the various topics building on what was known to what we are now finding out might be more effective, or pointing out the major questions in the field and adding new developments in our attempts to answer them. Neither of these are major problems with the review, but careful thought about making it flow a bit better might improve it further.
Response 2: The paragraph below that cites old literature and was part of section 8 has been moved to section 4.
“In C. elegans, a process of indefinite silencing of repetitive transgenes designed to be expressed in the germ line has been described by Kelly and co-authors in 1997 [50]. It was shown to be related to but distinct from the dsRNA-induced gene silencing [81].”
Point 3: The conclusion section is very disappointing. After introducing the reader to all these new exciting findings I am sure Dr. Grishok can elaborate a bit further on some of the potential implications and where things might be heading in the future.
Response 3: The conclusion section has been removed and substituted by the Outlook section, which highlights possible future directions of the discussed studies.
Point 4: Minor issues:
The following is a list of grammatical issues and/or typos that need to be modified by the author to improve the quality of the writing and the ability convey the correct information to the reader. The list may not be comprehensive so I urge the author to have the work re-read by a colleague.
Germline is used incorrectly throughout."Germ line" is a noun; "germline" is an adjective
Response 4: The reviewer’s diligent editing is very much appreciated; the manuscript has been modified accordingly. In addition, it was carefully proofread by a colleague.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe review article by A. Grishok provides a comprehensive overview of RNA- dependent epigenetic mechanisms in the nematode C. elegans. Subjects such as transgenerational inheritance are fully covered and overall, the manuscript is well-written and concise. I have no major comments besides a few minor typos and the suggestion to revise the title of the manuscript. Adding the term ‘RNA-dependent’ (or similar) to ‘Epigenetics Research’ would clarify that the content of this review article does not cover all epigenetic mechanisms in C. elegans but is rather focused on RNA-dependent processes.
Found typos:
Line 38: ‘is’ instead of ‘in’
Line 248: ‘not’ instead of ‘nor’
Author Response
Response to Reviewer 2 Comments
Point 1: The review article by A. Grishok provides a comprehensive overview of RNA- dependent epigenetic mechanisms in the nematode C. elegans. Subjects such as transgenerational inheritance are fully covered and overall, the manuscript is well-written and concise. I have no major comments besides a few minor typos and the suggestion to revise the title of the manuscript. Adding the term ‘RNA-dependent’ (or similar) to ‘Epigenetics Research’ would clarify that the content of this review article does not cover all epigenetic mechanisms in C. elegans but is rather focused on RNA-dependent processes.
Response 1: The title of the manuscript has been revised to “Small RNAs Worm up Transgenerational Epigenetics Research”
Point 2: Found typos:
Line 38: ‘is’ instead of ‘in’ Line 248: ‘not’ instead of ‘nor’
Response 2: The typos have been corrected.
