MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity.
Transcription factors (TFs) play critical roles in specifying many aspects of neuronal cell fate including dendritic morphology. How TFs are accurately regulated during neuronal morphogenesis is not fully understood. Here, we show that LIM homeodomain protein MEC-3, the key TF for C. elegans PVD den...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-09-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1010941 |
| _version_ | 1797672702236950528 |
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| author | Jianxin Xie Wei Zou Madina Tugizova Kang Shen Xiangming Wang |
| author_facet | Jianxin Xie Wei Zou Madina Tugizova Kang Shen Xiangming Wang |
| author_sort | Jianxin Xie |
| collection | DOAJ |
| description | Transcription factors (TFs) play critical roles in specifying many aspects of neuronal cell fate including dendritic morphology. How TFs are accurately regulated during neuronal morphogenesis is not fully understood. Here, we show that LIM homeodomain protein MEC-3, the key TF for C. elegans PVD dendrite morphogenesis, is regulated by both alternative splicing and an E3 ubiquitin ligase. The mec-3 gene generates several transcripts by alternative splicing. We find that mbl-1, the orthologue of the muscular dystrophy disease gene muscleblind-like (MBNL), is required for PVD dendrite arbor formation. Our data suggest mbl-1 regulates the alternative splicing of mec-3 to produce its long isoform. Deleting the long isoform of mec-3(deExon2) causes reduction of dendrite complexity. Through a genetic modifier screen, we find that mutation in the E3 ubiquitin ligase EEL-1 suppresses mbl-1 phenotype. eel-1 mutants also suppress mec-3(deExon2) mutant but not the mec-3 null phenotype. Loss of EEL-1 alone leads to excessive dendrite branches. Together, these results indicate that MEC-3 is fine-tuned by alternative splicing and the ubiquitin system to produce the optimal level of dendrite branches. |
| first_indexed | 2024-03-11T21:34:03Z |
| format | Article |
| id | doaj.art-9c7eb064c5ca436990728b8992b9e9c1 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-03-11T21:34:03Z |
| publishDate | 2023-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-9c7eb064c5ca436990728b8992b9e9c12023-09-27T05:31:19ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042023-09-01199e101094110.1371/journal.pgen.1010941MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity.Jianxin XieWei ZouMadina TugizovaKang ShenXiangming WangTranscription factors (TFs) play critical roles in specifying many aspects of neuronal cell fate including dendritic morphology. How TFs are accurately regulated during neuronal morphogenesis is not fully understood. Here, we show that LIM homeodomain protein MEC-3, the key TF for C. elegans PVD dendrite morphogenesis, is regulated by both alternative splicing and an E3 ubiquitin ligase. The mec-3 gene generates several transcripts by alternative splicing. We find that mbl-1, the orthologue of the muscular dystrophy disease gene muscleblind-like (MBNL), is required for PVD dendrite arbor formation. Our data suggest mbl-1 regulates the alternative splicing of mec-3 to produce its long isoform. Deleting the long isoform of mec-3(deExon2) causes reduction of dendrite complexity. Through a genetic modifier screen, we find that mutation in the E3 ubiquitin ligase EEL-1 suppresses mbl-1 phenotype. eel-1 mutants also suppress mec-3(deExon2) mutant but not the mec-3 null phenotype. Loss of EEL-1 alone leads to excessive dendrite branches. Together, these results indicate that MEC-3 is fine-tuned by alternative splicing and the ubiquitin system to produce the optimal level of dendrite branches.https://doi.org/10.1371/journal.pgen.1010941 |
| spellingShingle | Jianxin Xie Wei Zou Madina Tugizova Kang Shen Xiangming Wang MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity. PLoS Genetics |
| title | MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity. |
| title_full | MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity. |
| title_fullStr | MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity. |
| title_full_unstemmed | MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity. |
| title_short | MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity. |
| title_sort | mbl 1 and eel 1 affect the splicing and protein levels of mec 3 to control dendrite complexity |
| url | https://doi.org/10.1371/journal.pgen.1010941 |
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