RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases.
Mitochondrial translation defects can be due to mutations affecting mitochondrial- or nuclear-encoded components. The number of known nuclear genes involved in mitochondrial translation has significantly increased in the past years. RCC1L (WBSCR16), a putative GDP/GTP exchange factor, has recently b...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-07-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1008923 |
| _version_ | 1797867511888216064 |
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| author | Aurelio Reyes Paola Favia Sara Vidoni Vittoria Petruzzella Massimo Zeviani |
| author_facet | Aurelio Reyes Paola Favia Sara Vidoni Vittoria Petruzzella Massimo Zeviani |
| author_sort | Aurelio Reyes |
| collection | DOAJ |
| description | Mitochondrial translation defects can be due to mutations affecting mitochondrial- or nuclear-encoded components. The number of known nuclear genes involved in mitochondrial translation has significantly increased in the past years. RCC1L (WBSCR16), a putative GDP/GTP exchange factor, has recently been described to interact with the mitochondrial large ribosomal subunit. In humans, three different RCC1L isoforms have been identified that originate from alternative splicing but share the same N-terminus, RCC1LV1, RCC1LV2 and RCC1LV3. All three isoforms were exclusively localized to mitochondria, interacted with its inner membrane and could associate with homopolymeric oligos to different extent. Mitochondrial immunoprecipitation experiments showed that RCC1LV1 and RCC1LV3 associated with the mitochondrial large and small ribosomal subunit, respectively, while no significant association was observed for RCC1LV2. Overexpression and silencing of RCC1LV1 or RCC1LV3 led to mitoribosome biogenesis defects that resulted in decreased translation. Indeed, significant changes in steady-state levels and distribution on isokinetic sucrose gradients were detected not only for mitoribosome proteins but also for GTPases, (GTPBP10, ERAL1 and C4orf14), and pseudouridylation proteins, (TRUB2, RPUSD3 and RPUSD4). All in all, our data suggest that RCC1L is essential for mitochondrial function and that the coordination of at least two isoforms is essential for proper ribosomal assembly. |
| first_indexed | 2024-04-09T23:42:28Z |
| format | Article |
| id | doaj.art-2eb8ce9ad3ec4bdaaa9a99669d24020f |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-09T23:42:28Z |
| publishDate | 2020-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-2eb8ce9ad3ec4bdaaa9a99669d24020f2023-03-18T05:31:58ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042020-07-01167e100892310.1371/journal.pgen.1008923RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases.Aurelio ReyesPaola FaviaSara VidoniVittoria PetruzzellaMassimo ZevianiMitochondrial translation defects can be due to mutations affecting mitochondrial- or nuclear-encoded components. The number of known nuclear genes involved in mitochondrial translation has significantly increased in the past years. RCC1L (WBSCR16), a putative GDP/GTP exchange factor, has recently been described to interact with the mitochondrial large ribosomal subunit. In humans, three different RCC1L isoforms have been identified that originate from alternative splicing but share the same N-terminus, RCC1LV1, RCC1LV2 and RCC1LV3. All three isoforms were exclusively localized to mitochondria, interacted with its inner membrane and could associate with homopolymeric oligos to different extent. Mitochondrial immunoprecipitation experiments showed that RCC1LV1 and RCC1LV3 associated with the mitochondrial large and small ribosomal subunit, respectively, while no significant association was observed for RCC1LV2. Overexpression and silencing of RCC1LV1 or RCC1LV3 led to mitoribosome biogenesis defects that resulted in decreased translation. Indeed, significant changes in steady-state levels and distribution on isokinetic sucrose gradients were detected not only for mitoribosome proteins but also for GTPases, (GTPBP10, ERAL1 and C4orf14), and pseudouridylation proteins, (TRUB2, RPUSD3 and RPUSD4). All in all, our data suggest that RCC1L is essential for mitochondrial function and that the coordination of at least two isoforms is essential for proper ribosomal assembly.https://doi.org/10.1371/journal.pgen.1008923 |
| spellingShingle | Aurelio Reyes Paola Favia Sara Vidoni Vittoria Petruzzella Massimo Zeviani RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases. PLoS Genetics |
| title | RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases. |
| title_full | RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases. |
| title_fullStr | RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases. |
| title_full_unstemmed | RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases. |
| title_short | RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases. |
| title_sort | rcc1l wbscr16 isoforms coordinate mitochondrial ribosome assembly through their interaction with gtpases |
| url | https://doi.org/10.1371/journal.pgen.1008923 |
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