Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.
BACKGROUND: Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous s...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3623870?pdf=render |
| _version_ | 1818791354257375232 |
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| author | Tomáš Venit Rastislav Dzijak Alžběta Kalendová Michal Kahle Jana Rohožková Volker Schmidt Thomas Rülicke Birgit Rathkolb Wolfgang Hans Alexander Bohla Oliver Eickelberg Tobias Stoeger Eckhard Wolf Ali Önder Yildirim Valérie Gailus-Durner Helmut Fuchs Martin Hrabě de Angelis Pavel Hozák |
| author_facet | Tomáš Venit Rastislav Dzijak Alžběta Kalendová Michal Kahle Jana Rohožková Volker Schmidt Thomas Rülicke Birgit Rathkolb Wolfgang Hans Alexander Bohla Oliver Eickelberg Tobias Stoeger Eckhard Wolf Ali Önder Yildirim Valérie Gailus-Durner Helmut Fuchs Martin Hrabě de Angelis Pavel Hozák |
| author_sort | Tomáš Venit |
| collection | DOAJ |
| description | BACKGROUND: Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. CONCLUSION/SIGNIFICANCE: We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes. |
| first_indexed | 2024-12-18T15:10:01Z |
| format | Article |
| id | doaj.art-335edc2707c84f9b9b141223b512bfed |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-18T15:10:01Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-335edc2707c84f9b9b141223b512bfed2022-12-21T21:03:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6140610.1371/journal.pone.0061406Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.Tomáš VenitRastislav DzijakAlžběta KalendováMichal KahleJana RohožkováVolker SchmidtThomas RülickeBirgit RathkolbWolfgang HansAlexander BohlaOliver EickelbergTobias StoegerEckhard WolfAli Önder YildirimValérie Gailus-DurnerHelmut FuchsMartin Hrabě de AngelisPavel HozákBACKGROUND: Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. CONCLUSION/SIGNIFICANCE: We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes.http://europepmc.org/articles/PMC3623870?pdf=render |
| spellingShingle | Tomáš Venit Rastislav Dzijak Alžběta Kalendová Michal Kahle Jana Rohožková Volker Schmidt Thomas Rülicke Birgit Rathkolb Wolfgang Hans Alexander Bohla Oliver Eickelberg Tobias Stoeger Eckhard Wolf Ali Önder Yildirim Valérie Gailus-Durner Helmut Fuchs Martin Hrabě de Angelis Pavel Hozák Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus. PLoS ONE |
| title | Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus. |
| title_full | Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus. |
| title_fullStr | Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus. |
| title_full_unstemmed | Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus. |
| title_short | Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus. |
| title_sort | mouse nuclear myosin i knock out shows interchangeability and redundancy of myosin isoforms in the cell nucleus |
| url | http://europepmc.org/articles/PMC3623870?pdf=render |
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