Multiple Copies of microRNA Binding Sites in Long 3′UTR Variants Regulate Axonal Translation
Rapid responses to changes within subcellular compartments of highly polarized cells, such as neuron axons, depend on local translation and post-transcriptional regulation. The mechanism by which microRNAs (miRNAs) regulate this process is not fully understood. Here, using live cell imaging and RNA...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/2/233 |
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| author | Luba Farberov Ariel Ionescu Yazeed Zoabi Guy Shapira Amjd Ibraheem Yosi Azan Eran Perlson Noam Shomron |
| author_facet | Luba Farberov Ariel Ionescu Yazeed Zoabi Guy Shapira Amjd Ibraheem Yosi Azan Eran Perlson Noam Shomron |
| author_sort | Luba Farberov |
| collection | DOAJ |
| description | Rapid responses to changes within subcellular compartments of highly polarized cells, such as neuron axons, depend on local translation and post-transcriptional regulation. The mechanism by which microRNAs (miRNAs) regulate this process is not fully understood. Here, using live cell imaging and RNA sequencing analysis, we demonstrated how miRNAs can differentially control hundreds of transcripts at the subcellular level. We demonstrated that the seed match length of the miRNA target-sequence regulates both mRNA stability and protein translation rates. While longer seed matches have an increased inhibitory effect, transcriptome analysis did not reveal differences in seed match length between axonal and somata mRNAs of motor neurons. However, mRNA variants with longer 3′UTR are enriched in axons and contain multiple repeats of specific miRNA target sequences. Finally, we demonstrated that the long 3′UTR mRNA variant of the motor protein Kif5b is enriched explicitly in motor neuron axons and contains multiple sequence repeats for binding miR-129-5p. This subsequently results in the differential post-transcriptional regulation of kif5b and its synthesis in axons. Thus, we suggest that the number of miRNA binding sites at the 3′UTR of the mRNA, rather than the miRNA seed match length, regulates the axonal transcriptome. |
| first_indexed | 2024-03-09T13:12:51Z |
| format | Article |
| id | doaj.art-b5cc36437b7c41eca288d72a4a9ce8d3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T13:12:51Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b5cc36437b7c41eca288d72a4a9ce8d32023-11-30T21:39:28ZengMDPI AGCells2073-44092023-01-0112223310.3390/cells12020233Multiple Copies of microRNA Binding Sites in Long 3′UTR Variants Regulate Axonal TranslationLuba Farberov0Ariel Ionescu1Yazeed Zoabi2Guy Shapira3Amjd Ibraheem4Yosi Azan5Eran Perlson6Noam Shomron7Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelSackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelSackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelSackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelSackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelSackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelSackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelSackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, IsraelRapid responses to changes within subcellular compartments of highly polarized cells, such as neuron axons, depend on local translation and post-transcriptional regulation. The mechanism by which microRNAs (miRNAs) regulate this process is not fully understood. Here, using live cell imaging and RNA sequencing analysis, we demonstrated how miRNAs can differentially control hundreds of transcripts at the subcellular level. We demonstrated that the seed match length of the miRNA target-sequence regulates both mRNA stability and protein translation rates. While longer seed matches have an increased inhibitory effect, transcriptome analysis did not reveal differences in seed match length between axonal and somata mRNAs of motor neurons. However, mRNA variants with longer 3′UTR are enriched in axons and contain multiple repeats of specific miRNA target sequences. Finally, we demonstrated that the long 3′UTR mRNA variant of the motor protein Kif5b is enriched explicitly in motor neuron axons and contains multiple sequence repeats for binding miR-129-5p. This subsequently results in the differential post-transcriptional regulation of kif5b and its synthesis in axons. Thus, we suggest that the number of miRNA binding sites at the 3′UTR of the mRNA, rather than the miRNA seed match length, regulates the axonal transcriptome.https://www.mdpi.com/2073-4409/12/2/233KIF5BmiR-129-5paxons3′UTRseedRNA localization |
| spellingShingle | Luba Farberov Ariel Ionescu Yazeed Zoabi Guy Shapira Amjd Ibraheem Yosi Azan Eran Perlson Noam Shomron Multiple Copies of microRNA Binding Sites in Long 3′UTR Variants Regulate Axonal Translation Cells KIF5B miR-129-5p axons 3′UTR seed RNA localization |
| title | Multiple Copies of microRNA Binding Sites in Long 3′UTR Variants Regulate Axonal Translation |
| title_full | Multiple Copies of microRNA Binding Sites in Long 3′UTR Variants Regulate Axonal Translation |
| title_fullStr | Multiple Copies of microRNA Binding Sites in Long 3′UTR Variants Regulate Axonal Translation |
| title_full_unstemmed | Multiple Copies of microRNA Binding Sites in Long 3′UTR Variants Regulate Axonal Translation |
| title_short | Multiple Copies of microRNA Binding Sites in Long 3′UTR Variants Regulate Axonal Translation |
| title_sort | multiple copies of microrna binding sites in long 3 utr variants regulate axonal translation |
| topic | KIF5B miR-129-5p axons 3′UTR seed RNA localization |
| url | https://www.mdpi.com/2073-4409/12/2/233 |
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