Matrix: rps3 translation/ DNA repair (PTHR1170)

ValWood commented 5 years ago

I see there are lots of papers proposing may alternative roles for rps3 https://www.uniprot.org/uniprot/P23396 but I don't believe them ;)

All of the DNA repair related ones i looked at are in vitro assay.

I can see why these annotations might want to be kept but maybe this shouldn't be PAINTED until there is some really good evidence for these multiple roles.

It is also assayed in S. cerevisiae and has DNA endonuclease activity (in vitro). MAybe it is a ribonuclease. I don't see anything recording rps3 in association with DNA in yeast, or having a physiological role in DNA repair.

If this role were present in yeast we would likely know this.... (the assay was from 2001)

pgaudet commented 5 years ago

I think there is some strange isoform splitting with this one ???

ValWood commented 5 years ago

I don't see any good evidence though?

In vitro binding to damaged DNA? http://amigo.geneontology.org/amigo/reference/PMID:18610840

I don't think this can be used for positive regulation of repair http://amigo.geneontology.org/amigo/reference/PMID:18610840 if this is true, it could b e preventing damage, there is no experiment to show a role in repair

The title is "Damage surveillance"

Also this one again in vitro. No papers seem to show that this is functionally relevent, and the papers look quite dodgy! http://amigo.geneontology.org/amigo/reference/PMID:18973764 This one is Dec 2008.

I looked at quite a few of these old papers implicating rps3 in repair and I don't think they seem sound... I will ask some DNA repair people here...

(I do think there is isoform splitting in ribosomal proteins but it is mainly translation/ribosome assembly)

ValWood commented 5 years ago

Actually there are quite a few papers but I don't see any good evidence yet , but I only checked about 4 or 5 so I will create an exception for the time being, and see if I can find out what people think about this currently.

[25.] D.M.I. Wilson, W.A. Deutsch, M.R. Kelley, Drosophila ribosomal protein S3 contains an activity that cleaves DNA at apurinic/apyrimidinic sites, J. Biol. Chem. 269 (1994) 25359–25364.

[26] C.Y. Jang, J.Y. Lee, J. Kim, RpS3 a DNA repair endonuclease and ribosomal protein, is involved in apoptosis, FEBS Lett. 560 (2004) 81–85.

[27] S. Yadavilli, V. Hedge, W.A. Deutsch, Translocation of human ribosomal protein S3 to site of DNA damage is dependent on ERK-mediated phosphorylation following genotoxic stress, DNA Repair 6 (2007) 1453– 1462.

[28] S.H. Kim, J. Kim, Reduction of invasion in human fibrosarcoma cells by ribosomal protein S3 in conjunction with Nm23-H1 and ERK, Biochim. Biophys. Acta 1763 (2006) 823–832.

[29] H. Naora, H. Naora, Involvement of ribosomal proteins in regulating cell growth and apoptosis: translational modulation or recruitment for extraribosomal activity? Immunol. Cell. Biol. 77 (1999) 197–205.

[30] H. Naora, I. Takai, M. Adachi, H. Naora, Altered cellular responses by varying expression of a ribosomal protein gene: sequential coordination of enhancement and suppression of ribosomal protein S3a gene expression induces apoptosis, J. Cell Biol. 141 (1998) 741–753.

[31] F. Neumann, U. Krawinkel, Constitutive expression of human ribosomal protein L7 arrests the cell cycle in G1and induces apoptosis in Jurkat T-lymphoma cells, Exp. Cell Res. 230 (1997) 252–261.

[32] D.M.I. Wilson, W.A. Deutsch, M.R. Kelley, Cloning of the Drosophila ribosomal protein S3: another multifunctional ribosomal protein with AP endonuclease DNA repair activity, Nucleic Acid Res. 21 (1993) 2516.

[33] A. Yacoub, L. Augeri, M.R. Kelley, P.W. Doetsch, W.A. Deutsch, A Drosophila ribosomal protein contains 8-oxoguanine and abasic site DNA repair activities, EMBO J. 15 (1996) 2306–2312.

[34] V. Hegde, M.R. Kelley, Y. Xu, I.S. Mian, W.A. Deutsch, Conversion of the bifunctional 8-oxoguanine/– apurinic/apyrimidinic DNA repair activities of Drosophila ribosomal protein S3 into the human S3 monofunctional - elimination catalyst through a single amino acid change, J. Biol. Chem. 276 (2001) 27591–27596.

[35] M. Sandigursky, A. Yacoub, M.R. Kelley, W.A. Deutsch, W.A. Franklin, The Drosophila ribosomal protein S3 contains a DNA deoxyribophosphodiesterase (dRpase) activity, J. Biol. Chem. 272 (1997) 17480–17484.

[36] W.A. Deutsch, A. Yacoub, P. Jaruga, T.H. Zastawny, M. Dizdaroglu, Character

[37] J. Kim, L.S. Chubatsu, A. Admon, J. Stahl, R. Fellous, S. Linn, Implication of mammalian ribosomal protein S3 in the processing of DNA damage, J. Biol. Chem. 270 (1995) 13620–13629.

[38] V. Hegde, M. Wang, W.A. Deutsch, Human ribosomal protein S3 interacts with DNA base excision repair proteins hAPE1/Ref-1 and hOGG1, Biochemistry 43 (2004) 14211–14217.

[39] V. Hegde, M.Wang,W.A. Deutsch, Characterization of human ribosomal protein S3 binding to 7,8-dihydro-8-oxoguanine and abasic sites by surface plasmon resonance, DNA Repair 3 (2004) 121–126.

[40] V. Hegde, M. Wang, I.S. Mian, L. Spyres, W.A. Deutsch, The high binding affinity of human ribosomal protein S3 to 7-8-dihydro-8-oxoguanine is abrogated by a single amino acid change, DNA Repair 5 (2006) 810–815.

[41] V. Hegde, S. Yadavilli, W.A. Deutsch, Knock-down of ribosomal protein S3 protects human cells from genotoxic stress, DNA Repair 6 (2007) 94–99. [42] E. Dogliotti, P. Fortini, B. Pascucci, E. Parlanti, The mechanism of swi

ValWood commented 5 years ago

Flybase entry was reviewed in march 2019 and is considered to be bot a ribosomal protein and a DNA-formamidopyrimidine glycosylase (3.2.2.23) and a DNA-(apurinic or apyrimidinic site) lyase (4.2.99.18)

Quite a collection of functions. I'm not sure I believe all of this is packed into a 250 amino acid protein - but at present according to the data this is a truly multifunctional protein.....

http://flybase.org/reports/FBgn0002622.html

@hattrill

ValWood commented 5 years ago

Hell,, this protein is doing everything, it's the new P53!

The DNA repair domain of human rpS3 protects against photoaging by removing cyclobutane pyrimidine dimers. Yang HW, Kim HD, Kim J. FEBS Lett. 2019 Jun 10. doi: 10.1002/1873-3468.13479. [Epub ahead of print] PMID: 31180576

Ribosomal protein S3 localizes on the mitotic spindle and functions as a microtubule associated protein in mitosis. Jang CY, Kim HD, Zhang X, Chang JS, Kim J.

Biochem Biophys Res Commun. 2012 Dec 7;429(1-2):57-62. doi: 10.1016/j.bbrc.2012.10.093. Epub 2012 Nov 3. PMID: 23131551

Ribosomal protein S3 interacts with TRADD to induce apoptosis through caspase dependent JNK activation. Jang CY, Kim HD, Kim J.

Biochem Biophys Res Commun. 2012 May 11;421(3):474-8. doi: 10.1016/j.bbrc.2012.04.020. Epub 2012 Apr 9. PMID: 22510408

Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance. Kim Y, Kim HD, Kim J.

Biochim Biophys Acta. 2013 Dec;1833(12):2943-2952. doi: 10.1016/j.bbamcr.2013.07.015. Epub 2013 Jul 30. PMID: 23911537

Ribosomal protein S3 (rpS3) secreted from various cancer cells is N-linked glycosylated.

Kim Y, Lee MS, Kim HD, Kim J. Oncotarget. 2016 Dec 6;7(49):80350-80362. doi: 10.18632/oncotarget.10180. PMID: 27384988

See a pattern here?

ValWood commented 5 years ago

Nucleic Acids Res. 2017 Apr 20;45(7):3833-3843. doi: 10.1093/nar/gkx052. Recognition but no repair of abasic site in single-stranded DNA by human ribosomal uS3 protein residing within intact 40S subunit.

From the introduction of a 2017 paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397187/

It is currently believed that many ribosomal proteins (RPs) not only play roles in translation as constituents of the ribosome but also execute extra-ribosomal functions implicated in various cellular processes besides protein synthesis (for review, see (1–3)). However, these additional functions have been discovered mainly for isolated RPs that are outside of ribosomes. To our knowledge, involvement of ribosome-bound RPs in extra-ribosomal functions has been suggested only for two eukaryotic RPs, RACK1 and L13a. The former has a very specific structure enabling its binding to other proteins such as protein kinases and membrane receptors, which can link the ribosome to signaling pathways (for review, see (1,4)). RP L13a regulates ceruloplasmin mRNA translation; in response to a specific signal, it is phosphorylated and leaves the ribosome (which is viewed as a depot for L13a when its regulatory function is not concerned) to bind to the 3΄-untranslated region of the mRNA and stop its translation (5).

One of the most studied eukaryotic RPs is uS3, a key player in translation initiation on the small (40S) ribosomal subunit. When not bound to ribosomes, uS3 shows a number of activities unrelated to translation including those in the regulation of the genes controlled by NF-κB transcription factor and in DNA repair (reviewed in (6)). A number of issues concerning the latter implication of uS3 remain obscure, for example, it is unknown which kinds of DNA sequences or structural motifs preferably interact with uS3, and it is largely unclear when and where this ribosomal protein could contribute to DNA repair in the cell.

ValWood commented 5 years ago

I suggest for this one I create an exception, and the annotations stay if the data is reasonable- but it isn't painted unless there is in vivo evidence for such a role....

hattrill commented 5 years ago

It must be magic! It must be one of those moonlighting proteins that we hear so much about!

ValWood commented 5 years ago

I guess these ribosomal proteins can get up to all sorts when the rest of the ribosome isn't looking ;)

It has a KH domain so in-vitro binding to damaged (i.e single stranded) DNA isn't altogether unexpected...

hattrill commented 5 years ago

@sjm41 - I know that you have an interest in lyases and ribosomes.....what do you think? This should be your favourite fly gene?

sjm41 commented 5 years ago

Glad you found the fly papers on this - there's been a fair bit of (not so recent) work on this protein: http://flybase.org/reports/FBgn0002622.html#pubs

These GO tickets are also related - I think we fixed all issues reported: https://github.com/geneontology/go-ontology/issues/13409 https://github.com/geneontology/go-ontology/issues/15308

ValWood commented 5 years ago

@sjm41 I made an exception, but do you think this really is an DNA-lyase physiologically? I could not find any real evidence for such a role. In fact, the most recent paper (above) states that for human this activity is dependent on the protein being ex-ribosome. Then one must assume transported to the nucleus (at least if acting outside mitosis when most repair occurs) . Also, it is shown not to be part of the general repair pathways. Some papers say it does not bind damaged DNA with greater affinity than undamaged. There is lots of conflicting data and no cohesive picture from what I looked at so far. However, I only looked at the human papers, not the fly.

sjm41 commented 5 years ago

Hi. I can't speak for the non-fly work, but I am persuaded by results in these 3 fly papers: Wilson et al (1994) FBrf0076708/PMID:7929231 (FB GO annotation from this) - also shows nuclear localization Yacoub et al (1996) FBrf0087792/PMID:8641296 (FB GO annotation from this) - also shows complementation by Dmel RpS3 of an E.coli strains deficient in DNA repair/AP lyases Kelley et al (2001) FBrf0134781/PMID:11182542

pgaudet commented 5 years ago

@marcfeuermann and I have reviewed the family and kept the DNA endonuclease activity for RPS3.

pgaudet commented 5 years ago

Comment for Flybase: RPS3 is an lyase, not a glycosylase (please fix annotation from 8641296). In the Uniprot entry for the human gene (P23396), it is stated that it regulates the N-glycosylase activity of the base excision protein OGG1 (PMID:15518571). Can you please review?

Thanks, Pascale

geneontology / go-annotation

Matrix: rps3 translation/ DNA repair (PTHR1170) #2464