Talk:Rubicon (protein)

Did you know nomination

The following is an archived discussion of the DYK nomination of the article below. Please do not modify this page. Subsequent comments should be made on the appropriate discussion page (such as this nomination's talk page, the article's talk page or Wikipedia talk:Did you know), unless there is consensus to re-open the discussion at this page. No further edits should be made to this page.

The result was: promoted by SL93 (talk) 00:21, 29 August 2022 (UTC)

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Atomic structure of Rubicon (red) bound to switch molecule Rab7

• ... that deleting the protein Rubicon (shown) increases lifespan and reduces age-related disease in mice, flies, and worms? Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381146/

  From the abstract: "Consistent with this idea, knockdown of Rubicon extends worm and fly lifespan and ameliorates several age-associated phenotypes. Tissue-specific experiments reveal that Rubicon knockdown in neurons has the greatest effect on lifespan. Rubicon knockout mice exhibits reductions in interstitial fibrosis in kidney and reduced α-synuclein accumulation in the brain."

  • ALT1: ... that genetically crossing (out) the protein Rubicon (shown) reduces hallmarks of aging in roundworms, fruit flies, and mice? Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381146/

    From the abstract: "Consistent with this idea, knockdown of Rubicon extends worm and fly lifespan and ameliorates several age-associated phenotypes. Tissue-specific experiments reveal that Rubicon knockdown in neurons has the greatest effect on lifespan. Rubicon knockout mice exhibits reductions in interstitial fibrosis in kidney and reduced α-synuclein accumulation in the brain."

  • ALT2: ... that when crossing out Rubicon (shown), the time to die is cast later in roundworms and female fruit flies? Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381146/

    From the abstract: "Consistent with this idea, knockdown of Rubicon extends worm and fly lifespan and ameliorates several age-associated phenotypes. Tissue-specific experiments reveal that Rubicon knockdown in neurons has the greatest effect on lifespan. Rubicon knockout mice exhibits reductions in interstitial fibrosis in kidney and reduced α-synuclein accumulation in the brain."

  • ALT3: ... that genetic deletion of Rubicon reduces hallmarks of aging in roundworms, fruit flies, and mice? Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381146/

    Frome the abstract: "Consistent with this idea, knockdown of Rubicon extends worm and fly lifespan and ameliorates several age-associated phenotypes. Tissue-specific experiments reveal that Rubicon knockdown in neurons has the greatest effect on lifespan. Rubicon knockout mice exhibits reductions in interstitial fibrosis in kidney and reduced α-synuclein accumulation in the brain."

• • Reviewed:

Created by Prodigiousfool (talk). Self-nominated at 19:52, 21 June 2022 (UTC).

• It's a very interesting fact and the source on it is excellent. Unfortunately, I don't think the article qualifies per WP:DYKRULES as it was neither created, expanded fivefold, or promoted to GA status within seven days before the nomination. PianoUpMyNose (talk) 13:03, 27 June 2022 (UTC)
  • It was moved to mainspace on June 20, so it qualifies. I'm currently in the process of reviewing it in detail, though it takes quite some time as it is all rather technical. TompaDompa (talk) 13:16, 27 June 2022 (UTC)
    • You're right. This was my first review and I completely missed that. My mistake. PianoUpMyNose (talk) 19:08, 30 June 2022 (UTC)

General: Article is new enough and long enough
New enough: Long enough:

Policy: Article is sourced, neutral, and free of copyright problems
Adequate sourcing: Neutral: Free of copyright violations, plagiarism, and close paraphrasing:

Hook eligibility:

• Cited: - What's cited is that Rubicon deletion increases lifespan in (female fruit) flies and (round)worms and reduces (hallmarks of) age-related disease in mice. The current hook phrasing implies that it also increases lifespan in mice.
• Interesting: - The proposed hook is rather dull. For a protein called Rubicon, I would suggest seizing the opportunity to make a humorous reference to crossing the Rubicon. Two possibilities off the top of my head would be "crossing out Rubicon" (i.e. performing a gene knockout) and making a pun on the multiple meanings of "die" (considering the English translation of Alea iacta est). Some other punny reference to Julius Caesar could also work.

Image: Image is freely licensed, used in the article, and clear at 100px.
Freely licensed: Used in article: Clear at 100px:

QPQ: None required.

Overall: Article moved to mainspace on 20 June, and is well beyond the required minimum length. All sources are, as far as I can tell, reliable. Earwig reveals no copyvio and I didn't spot any instances of unacceptably WP:Close paraphrasing. The picture meets the requirements, inasmuch as any ribbon diagram of a protein can be "clear", though it doesn't aid the readers' understanding much and I think this might be better as a "quirky" DYK entry (typically placed last) than as the top entry—but I'll leave that decision to the promoter (not that kind). This is the nominator's first nomination, so they are QPQ exempt. On account of this all being rather technical, I'll never be able to entirely rule out having missed some disqualifying issue with the content and will eventually just have too WP:Assume good faith. That being said, spot-checking did reveal some issues that will need to be addressed. Since this is basically all WP:Biomedical information, the sourcing requirements are fairly strict. My comments:

• one of the few known negative regulators of autophagy – "one of the few known" is key here, and I didn't find that in the cited source. I did however find Rubicon is one of very few known broadly acting negative regulators of autophagy in reference 8 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382272/).
• cytosolic materials should probably be "cellular components".
• impairs the autophagosome-lysosome fusion step of autophagy through inhibition of PI3KC3-C2 – It seems to me that the source to cite here is reference 8 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382272/), which says "Rubicon disrupts autophagosome–lysosome fusion by inhibiting the class III phosphatidylinositol 3-kinase complex 2 (PI3KC3-C2)" rather than the sources it cites in the spirit of WP:Cite reviews, don't write them. It would at any rate have saved me as DYK reviewer a considerable amount of time in checking that the claims in the article are supported by the sources.
• Lysosome should be linked.
• Reference 13 and 14 are duplicates (both link to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381146). So are reference 5 and 12 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664389); reference 7, 10, and 25 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450660); and reference 8, 20, and 23 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382272).
• The WP:LEAD says Rubicon has been shown to positively regulate LC3-associated phagocytosis (LAP) and LC3-associated endocytosis (LANDO) whereas the body says Rubicon is required for LC3-associated phagocytosis (LAP) and LC3-associated endocytosis (LANDO). Is it a positive regulator or required?
• direct interaction with multiple effector molecules – is "effector molecules" really the right term here?
• The Rubicon homology domain is rich in histidine and cysteine residues – cysteine, yes, but histidine? Of the four zinc fingers, two have 3:1 cysteine:histidine ratios and the other two 4:0.
• The C-terminal Rubicon homology domain mediates interaction with Rab7, and is shared by other RH domain-containing autophagy regulatory proteins, including PLEKHM1 and Pacer (also known as RUBCNL, Rubicon-like Autophagy Enhancer). is unsourced, though I think reference 8 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382272/) would do.
• The sources discuss inhibition of autophagosome maturation a great deal, but this article doesn't mention it at all.
• conformational should link to protein conformation.
• Rubicon recruits PI3KC3 to phagosomes – what the source says is that in the absence of Rubicon, Beclin1, UVRAG, and VPS34 recruitment was reduced, suggesting that Rubicon plays a role in the retention of the complex at the LAPosome.
• in some cases exacerbate infection – this is a statement about the clinical course of the infection. What the source says is that it facilitates viral replication. More viral replication does not necessarily translate to a worse clinical infection.
• Rubicon suppresses interferon and cytokine responses – interferons are a subgroup of cytokines, so this is phrasing is a bit odd. I would also link interferon and cytokine.
• The sentence Since reduced autophagy is associated with decreased lifespan and increase susceptibility to disease, therapeutic modulation of Rubicon is of great interest in aging and age-related diseases. categorically needs to be sourced.
• I can maybe accept using "flies" to refer to Drosophila melanogaster—though I would really prefer "fruit flies"—but not using "worms" to refer to C. elegans since the reader is likely to interpret it as meaning earthworms rather than roundworms if they don't look up C. elegans, which they are not likely to do. The names of the species should also be rendered in italics.
• Rubicon knockout increases lifespan in worms (C. elegans) and flies (D. melanogaster) through modulation of autophagy. – The source attributes this to autophagy modulation for the former (C. elegans Rubicon regulates lifespan via modulating autophagy.) but not for the latter as far as I can see. Moreover, this only applies to female D. melanogaster, according to the source (whole body dRubicon knockdown slightly but significantly extended the lifespan in female specific manner).
• The mutation that causes Salih ataxia should be further explained as a single-nucleotide deletion and a link to frameshift mutation should be included somewhere.
• the Rubicon C-Terminal domain and RH domain – the RH domain is the C-terminal domain, no?
• This is consistent with subsequent structural studies investigating the Rubicon:Rab7 interface. – this seems to be your WP:ANALYSIS.
• See Also should be "See also" with a lowercase "a".

Ping Prodigiousfool. TompaDompa (talk) 23:08, 27 June 2022 (UTC)

• Following edits by Prodigiousfool and a few additional ones by me, the content-related issues have now been sufficiently resolved. The article still doesn't discuss authophagosome maturation, but that's not required for DYK (it would however be necessary to cover that aspect if this were nominated for WP:Good article status). A better hook and this is good to go. TompaDompa (talk) 12:37, 1 July 2022 (UTC)
  • @TompaDompa: thanks for your attention. I've updated the hook above per suggestions and discussion on the Talk page. I'll try to work on the article to discuss autophagosome maturation in the near future; that's definitely a good idea. - Prodigiousfool
    • For the record, the talk page in question is Template talk:Did you know nominations/Rubicon (protein) (not the article talk page). I've restored the old hook suggestion and labelled the new one ALT1 for ease of following the discussion. That being said, I don't think ALT1 is particularly "hooky" either; the idea is that the reader will be enticed to click the link to the article, which is kind of undercut by explaining the joke too much. I would suggest something along the lines of ... that when crossing out Rubicon, the time to die is cast later in roundworms and female fruit flies? to get a pun on crossing the Rubicon and Alea iacta est both. TompaDompa (talk) 14:35, 2 July 2022 (UTC)
      • @TompaDompa: Updated ALT1 based on your suggestion. I like the phrasing, though my intuition before was that something like that is too obfuscated for a general audience. I defer, of course, to your experience here! -- Prodigiousfool
        • Again, I've restored the previous version of ALT1 and labelled the edited version ALT2 for ease of following the discussion. I wouldn't say I'm all that experienced when it comes to DYK matters. Anyway: I agree that the hook is a bit opaque, but I think the double pun makes up for it. The point of the hook is after all to entice the reader to click the bolded link and read the article, and I would personally be more inclined to do so if I saw ALT2 on the main page than if it were slightly more clear but less humorous. However, before this appears on the WP:Main page somebody else will look at it to promote it to a prep or queue—and they may very well disagree with me if they find "the time to die is cast later" too awkward a phrasing and/or the pun on "the die is cast" too subtle. I wouldn't blame them, and it's precisely because there are additional layers of checking that I am comfortable approving it. With all that said: ALT2 is ready. TompaDompa (talk) 16:44, 7 July 2022 (UTC)

As discussed on the DYK talk page, it needs a new hook. Schwede66 09:41, 18 July 2022 (UTC)

I'd like to nominate ALT3: "... that genetic deletion of the protein Rubicon reduces hallmarks of aging in roundworms, fruit flies, and mice?". I know that TompaDompa finds this form uninspiring (see their comments on the similar ALT1), however I'd argue that both to scientific and general audiences this is an interesting piece of information. From a scientific perspective, this protein was discovered and its function elucidated quite recently, and as the article says it is a potential target for novel therapeutics. To a general audience, the concept of aging mitigation is likely of interest and the Rubicon article can provide a gateway to reading about multiple related topics, including autophagy. I don't think the fact that the results originate from model organisms detracts from the hook, especially given the lack of controlled aging trials in humans. — Preceding unsigned comment added by Prodigiousfool (talk • contribs) 05:29, 23 July 2022 (UTC)

The original hook and ALT1 and ALT2 all having been rejected on the DYK talk page, ALT3 needs to be reviewed. (I've edited the version just above so it matches what's given up top for the same ALT3.) BlueMoonset (talk) 22:50, 25 July 2022 (UTC)

I don't think the wording in ALT3 is not matched in the article. The article does not state that Rubicon's deletion increases the lifespan in mice (although other benefits are given) and the article says that it increases the lifespan of roundwords and fruit flies, not "reducing hallmarks of aging". I'm suggesting an ALT below:

ALT4: ... that genetic deletion of the protein Rubicon increases the lifespan of roundworms and fruit flies?

@Prodigiousfool and TompaDompa: Thoughts? Z1720 (talk) 23:47, 1 August 2022 (UTC)

@Z1720: I would contend that the 'hallmarks of aging' phrasing is consistent with the citation, as it does not imply actual aging, but I defer to your judgment here. – Prodigiousfool

As I indicated at WT:DYK, I don't think the fact that performing a specific knockout extends lifespans in Caenorhabditis elegans and female Drosophila melanogaster is terribly interesting in itself; these animals are used for genetic studies because it's practical (short lifespans and so on), and there is no reason to expect this to translate to humans (it doesn't even translate to male D. melanogaster). That being said, I'm not going to protest if somebody else approves such a hook. TompaDompa (talk) 19:17, 3 August 2022 (UTC)

@Prodigiousfool: My concern with ALT 3 was not that it was not reflected in the source, but rather that it is not present in the article itself. If hallmarks of aging is the prefered language, then that should be put in the article. @TompaDompa: I find ALT3/4 to be interesting, as increasing life in animals could have ramifications in other species, like himans. If you do not think ALT3/4 are interesting then please propose new ALTs. Z1720 (talk) 01:52, 6 August 2022 (UTC)

I'm not going to review this nomination but I do think that ALT4 is a decent hook. Can we go with it if there's no article/sourcing issues with it? Narutolovehinata5 (talk · contributions) 01:30, 7 August 2022 (UTC)

I support ALT4. Alternatively ALT5: ... that genetic deletion of the protein Rubicon is associated with reduction of aging-associated diseases in mice, roundworms, and fruit flies? I'd be happy with either being reviewed and putting this issue to rest. Tag Z1720, Narutolovehinata5. – Prodigiousfool

I haven't checked the article but I think ALT4 is a better hook since it's simpler. Narutolovehinata5 (talk · contributions) 03:40, 10 August 2022 (UTC)

@Narutolovehinata5: The article itself has already been reviewed. The only thing that is needed is a new hook. The difficulty with pages like this is coming up with a hook that is interesting without insinuating more significance than is warranted. In this case, the issue I have with ALT3/ALT4/ALT5 is that what would make it interesting is the implicit suggestion that this might have medical implications for humans, which is not warranted. To my eye, we're either making too strong a claim (if we are indeed implying that this could have implications for humans) or stating something that is rather dull (if we are not). Others might disagree, of course. Another angle that might be pursued in crafting an interesting hook is that the protein appears to have been independently discovered/characterized as part of investigations of autophagy[1] and Salih ataxia[2][3], though this is not currently mentioned in the article. By the way, I discovered this article which appears (I haven't read the article in detail) to contradict the article about Rubicon's role in LAP. This should be resolved. TompaDompa (talk) 21:13, 10 August 2022 (UTC)

... implicit suggestion that this might have medical implications for humans. Personally I didn't see that connection at all. Narutolovehinata5 (talk · contributions) 00:37, 11 August 2022 (UTC)

@TompaDompa: Just wanted to say I agree with Narutolovehinata5 that I don't see an implicit implication here. I am aware WP:MEDRS has somewhat higher sourcing requirements, but afaik an DYK hook simply must not be actively misleading and cited in the article. These aren't actively misleading, as the claim in the hooks is entirely correct. They're just hooky. Of course the whole science in this area (and in most areas) is done in hopes of eventually finding something that is useful for humans. But that this was achieved here is not claimed, and imo only tabloid papers would misquote it as such.

Totally unrelated, but out of curiosity: Prodigiousfool why are your signatures not timestamped? --LordPeterII (talk) 16:59, 20 August 2022 (UTC)

@LordPeterII: Glad there's agreement about the phrasing. Now how do we get this reviewed and finally closed!! No timestamps because I'm new to this and not sure how it works. Editing using the markup/source code editor (visual editor and reply buttons not working for me here), so manually adding signatures. Please LMK if there's a better way!! – Prodigiousfool

@Prodigiousfool: If you add four tildes (i.e. ~~~~) to the end of your comment, it turns into your signature including the timestamp when you save the page. Three for just the signature, five for just the timestamp. See WP:TILDE for details.

I cannot in good conscience approve a hook I don't think is interesting, but there's nothing stopping anyone else from approving ALT4 if they disagree (though it should really specify female fruit flies, in my opinion). Alternatively, you could try coming up with a hook that focuses on some different aspect, such as being independently discovered/characterized as part of investigations of autophagy (a universal process) and Salih ataxia (an extremely rare condition). TompaDompa (talk) 20:01, 20 August 2022 (UTC)

@Prodigiousfool: Ah I see, please use the 4 tildes as TompaDompa suggested – only that way a ping actually causes a notification to pop up (so just now I wasn't notified about you pinging me, although the ping was formatted correctly).

@TompaDompa: Ah, I understand now that you actually believe the hooks to be dull without the implications, rather than inappropriate (misread that). Well, in my opinion they're not dull (but then, I find many things interesting simply because they are unexpected); yet I'd feel a bit uncomfortable approving a hook you dislike. Regardless, I'll put yet another ALT below (adding "female"):

• ALT4a: ... that genetic deletion of the protein Rubicon increases the lifespan of roundworms and female fruit flies?

Someone else may approve it. --LordPeterII (talk) 22:36, 20 August 2022 (UTC)

Reviewer needed to check ALT4a. Thanks. BlueMoonset (talk) 00:10, 24 August 2022 (UTC)

- ALT4a checked and acceptable (did not check rest of article other than content and citation for ALT4a). starship.paint (exalt) 13:36, 27 August 2022 (UTC)