A translation-independent function of PheRS activates growth and proliferation in Drosophila
Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) not only load the appropriate amino acid onto their cognate tRNAs, but many of them also perform additional functions that are not necessarily related to their canonical activities. Phenylalanyl tRNA synthetase (PheRS/FARS) levels are elevated in mul...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2021-03-01
|
| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/14/3/dmm048132 |
| _version_ | 1819320461011451904 |
|---|---|
| author | Manh Tin Ho Jiongming Lu Dominique Brunßen Beat Suter |
| author_facet | Manh Tin Ho Jiongming Lu Dominique Brunßen Beat Suter |
| author_sort | Manh Tin Ho |
| collection | DOAJ |
| description | Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) not only load the appropriate amino acid onto their cognate tRNAs, but many of them also perform additional functions that are not necessarily related to their canonical activities. Phenylalanyl tRNA synthetase (PheRS/FARS) levels are elevated in multiple cancers compared to their normal cell counterparts. Our results show that downregulation of PheRS, or only its α-PheRS subunit, reduces organ size, whereas elevated expression of the α-PheRS subunit stimulates cell growth and proliferation. In the wing disc system, this can lead to a 67% increase in cells that stain for a mitotic marker. Clonal analysis of twin spots in the follicle cells of the ovary revealed that elevated expression of the α-PheRS subunit causes cells to grow and proliferate ∼25% faster than their normal twin cells. This faster growth and proliferation did not affect the size distribution of the proliferating cells. Importantly, this stimulation proliferation turned out to be independent of the β-PheRS subunit and the aminoacylation activity, and it did not visibly stimulate translation. This article has an associated First Person interview with the joint first authors of the paper. |
| first_indexed | 2024-12-24T11:19:56Z |
| format | Article |
| id | doaj.art-5a1dd63404214edabe795229f80da450 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-24T11:19:56Z |
| publishDate | 2021-03-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-5a1dd63404214edabe795229f80da4502022-12-21T16:58:16ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112021-03-0114310.1242/dmm.048132048132A translation-independent function of PheRS activates growth and proliferation in DrosophilaManh Tin Ho0Jiongming Lu1Dominique Brunßen2Beat Suter3 Institute of Cell Biology, University of Bern, Baltzerstrasse 4, Bern 3012, Switzerland Institute of Cell Biology, University of Bern, Baltzerstrasse 4, Bern 3012, Switzerland Institute of Cell Biology, University of Bern, Baltzerstrasse 4, Bern 3012, Switzerland Institute of Cell Biology, University of Bern, Baltzerstrasse 4, Bern 3012, Switzerland Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) not only load the appropriate amino acid onto their cognate tRNAs, but many of them also perform additional functions that are not necessarily related to their canonical activities. Phenylalanyl tRNA synthetase (PheRS/FARS) levels are elevated in multiple cancers compared to their normal cell counterparts. Our results show that downregulation of PheRS, or only its α-PheRS subunit, reduces organ size, whereas elevated expression of the α-PheRS subunit stimulates cell growth and proliferation. In the wing disc system, this can lead to a 67% increase in cells that stain for a mitotic marker. Clonal analysis of twin spots in the follicle cells of the ovary revealed that elevated expression of the α-PheRS subunit causes cells to grow and proliferate ∼25% faster than their normal twin cells. This faster growth and proliferation did not affect the size distribution of the proliferating cells. Importantly, this stimulation proliferation turned out to be independent of the β-PheRS subunit and the aminoacylation activity, and it did not visibly stimulate translation. This article has an associated First Person interview with the joint first authors of the paper.http://dmm.biologists.org/content/14/3/dmm048132aminoacyl trna synthetasephersfarsagrowth and proliferation control |
| spellingShingle | Manh Tin Ho Jiongming Lu Dominique Brunßen Beat Suter A translation-independent function of PheRS activates growth and proliferation in Drosophila Disease Models & Mechanisms aminoacyl trna synthetase phers farsa growth and proliferation control |
| title | A translation-independent function of PheRS activates growth and proliferation in Drosophila |
| title_full | A translation-independent function of PheRS activates growth and proliferation in Drosophila |
| title_fullStr | A translation-independent function of PheRS activates growth and proliferation in Drosophila |
| title_full_unstemmed | A translation-independent function of PheRS activates growth and proliferation in Drosophila |
| title_short | A translation-independent function of PheRS activates growth and proliferation in Drosophila |
| title_sort | translation independent function of phers activates growth and proliferation in drosophila |
| topic | aminoacyl trna synthetase phers farsa growth and proliferation control |
| url | http://dmm.biologists.org/content/14/3/dmm048132 |
| work_keys_str_mv | AT manhtinho atranslationindependentfunctionofphersactivatesgrowthandproliferationindrosophila AT jiongminglu atranslationindependentfunctionofphersactivatesgrowthandproliferationindrosophila AT dominiquebrunßen atranslationindependentfunctionofphersactivatesgrowthandproliferationindrosophila AT beatsuter atranslationindependentfunctionofphersactivatesgrowthandproliferationindrosophila AT manhtinho translationindependentfunctionofphersactivatesgrowthandproliferationindrosophila AT jiongminglu translationindependentfunctionofphersactivatesgrowthandproliferationindrosophila AT dominiquebrunßen translationindependentfunctionofphersactivatesgrowthandproliferationindrosophila AT beatsuter translationindependentfunctionofphersactivatesgrowthandproliferationindrosophila |