Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis
<p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons (MNs). There are no effective treatments and patients usually die within 2–5 years of diagnosis. Emerging commonalities between familial and sporadic cases of this complex mul...
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2022
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| _version_ | 1864513518668087296 |
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| author | Sophie Hawkins (18421377) |
| author2 | Seema C. Namboori (11031624) Ammarah Tariq (18421380) Catherine Blaker (18421383) Christine Flaxman (18421386) Nidhi S. Dey (18421389) Peter Henley (16296524) Andrew Randall (2601499) Alessandro Rosa (470248) Lawrence W. Stanton (6707191) Akshay Bhinge (173004) |
| author2_role | author author author author author author author author author author |
| author_facet | Sophie Hawkins (18421377) Seema C. Namboori (11031624) Ammarah Tariq (18421380) Catherine Blaker (18421383) Christine Flaxman (18421386) Nidhi S. Dey (18421389) Peter Henley (16296524) Andrew Randall (2601499) Alessandro Rosa (470248) Lawrence W. Stanton (6707191) Akshay Bhinge (173004) |
| author_role | author |
| dc.creator.none.fl_str_mv | Sophie Hawkins (18421377) Seema C. Namboori (11031624) Ammarah Tariq (18421380) Catherine Blaker (18421383) Christine Flaxman (18421386) Nidhi S. Dey (18421389) Peter Henley (16296524) Andrew Randall (2601499) Alessandro Rosa (470248) Lawrence W. Stanton (6707191) Akshay Bhinge (173004) |
| dc.date.none.fl_str_mv | 2022-07-12T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.stemcr.2022.05.019 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Upregulation_of_-catenin_due_to_loss_of_miR-139_contributes_to_motor_neuron_death_in_amyotrophic_lateral_sclerosis/25663731 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Genetics ALS microRNA miR-139 WNT FUS sporadic iPSC motor neurons |
| dc.title.none.fl_str_mv | Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons (MNs). There are no effective treatments and patients usually die within 2–5 years of diagnosis. Emerging commonalities between familial and sporadic cases of this complex multifactorial disorder include disruption to RNA processing and cytoplasmic inclusion bodies containing TDP-43 and/or FUS protein aggregates. Both TDP-43 and FUS have been implicated in RNA processing functions, including microRNA biogenesis, transcription, and splicing. In this study, we explore the misexpression of microRNAs in an iPSC-based disease model of FUS ALS. We identify the downregulation of miR-139, an MN-enriched microRNA, in FUS and sporadic ALS MN. We discover that miR-139 downregulation leads to the activation of canonical WNT signaling and demonstrate that the WNT transcriptional mediator β-catenin is a major driver of MN degeneration in ALS. Our results highlight the importance of homeostatic RNA networks in ALS.</p><h2>Other Information</h2> <p> Published in: Stem Cell Reports<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.stemcr.2022.05.019" target="_blank">https://dx.doi.org/10.1016/j.stemcr.2022.05.019</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_123ca61c4d2f7ce22b62835ea7af7be2 |
| identifier_str_mv | 10.1016/j.stemcr.2022.05.019 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25663731 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosisSophie Hawkins (18421377)Seema C. Namboori (11031624)Ammarah Tariq (18421380)Catherine Blaker (18421383)Christine Flaxman (18421386)Nidhi S. Dey (18421389)Peter Henley (16296524)Andrew Randall (2601499)Alessandro Rosa (470248)Lawrence W. Stanton (6707191)Akshay Bhinge (173004)Biological sciencesBiochemistry and cell biologyGeneticsALSmicroRNAmiR-139WNTFUSsporadiciPSCmotor neurons<p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons (MNs). There are no effective treatments and patients usually die within 2–5 years of diagnosis. Emerging commonalities between familial and sporadic cases of this complex multifactorial disorder include disruption to RNA processing and cytoplasmic inclusion bodies containing TDP-43 and/or FUS protein aggregates. Both TDP-43 and FUS have been implicated in RNA processing functions, including microRNA biogenesis, transcription, and splicing. In this study, we explore the misexpression of microRNAs in an iPSC-based disease model of FUS ALS. We identify the downregulation of miR-139, an MN-enriched microRNA, in FUS and sporadic ALS MN. We discover that miR-139 downregulation leads to the activation of canonical WNT signaling and demonstrate that the WNT transcriptional mediator β-catenin is a major driver of MN degeneration in ALS. Our results highlight the importance of homeostatic RNA networks in ALS.</p><h2>Other Information</h2> <p> Published in: Stem Cell Reports<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.stemcr.2022.05.019" target="_blank">https://dx.doi.org/10.1016/j.stemcr.2022.05.019</a></p>2022-07-12T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.stemcr.2022.05.019https://figshare.com/articles/journal_contribution/Upregulation_of_-catenin_due_to_loss_of_miR-139_contributes_to_motor_neuron_death_in_amyotrophic_lateral_sclerosis/25663731CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256637312022-07-12T03:00:00Z |
| spellingShingle | Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis Sophie Hawkins (18421377) Biological sciences Biochemistry and cell biology Genetics ALS microRNA miR-139 WNT FUS sporadic iPSC motor neurons |
| status_str | publishedVersion |
| title | Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis |
| title_full | Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis |
| title_fullStr | Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis |
| title_full_unstemmed | Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis |
| title_short | Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis |
| title_sort | Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis |
| topic | Biological sciences Biochemistry and cell biology Genetics ALS microRNA miR-139 WNT FUS sporadic iPSC motor neurons |