Cell environment shapes TDP-43 function with implications in neuronal and muscle disease
<jats:title>Abstract</jats:title><jats:p>TDP-43 (TAR DNA-binding protein 43) aggregation and redistribution are recognised as a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. As TDP-43 inclusions have recently been described in the muscle of inclusion body m...
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2023
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| Online Access: | https://hdl.handle.net/1721.1/147815 |
| _version_ | 1826205240366465024 |
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| author | Fraenkel, Ernest |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Fraenkel, Ernest |
| author_sort | Fraenkel, Ernest |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>TDP-43 (TAR DNA-binding protein 43) aggregation and redistribution are recognised as a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. As TDP-43 inclusions have recently been described in the muscle of inclusion body myositis patients, this highlights the need to understand the role of TDP-43 beyond the central nervous system. Using RNA-seq, we directly compare TDP-43-mediated RNA processing in muscle (C2C12) and neuronal (NSC34) mouse cells. TDP-43 displays a cell-type-characteristic behaviour targeting unique transcripts in each cell-type, which is due to characteristic expression of RNA-binding proteins, that influence TDP-43’s performance and define cell-type specific splicing. Among splicing events commonly dysregulated in both cell lines, we identify some that are TDP-43-dependent also in human cells. Inclusion levels of these alternative exons are altered in tissues of patients suffering from FTLD and IBM. We therefore propose that TDP-43 dysfunction contributes to disease development either in a common or a tissue-specific manner.</jats:p> |
| first_indexed | 2024-09-23T13:09:54Z |
| format | Article |
| id | mit-1721.1/147815 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:09:54Z |
| publishDate | 2023 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1478152023-02-01T03:28:31Z Cell environment shapes TDP-43 function with implications in neuronal and muscle disease Fraenkel, Ernest Massachusetts Institute of Technology. Department of Biological Engineering <jats:title>Abstract</jats:title><jats:p>TDP-43 (TAR DNA-binding protein 43) aggregation and redistribution are recognised as a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. As TDP-43 inclusions have recently been described in the muscle of inclusion body myositis patients, this highlights the need to understand the role of TDP-43 beyond the central nervous system. Using RNA-seq, we directly compare TDP-43-mediated RNA processing in muscle (C2C12) and neuronal (NSC34) mouse cells. TDP-43 displays a cell-type-characteristic behaviour targeting unique transcripts in each cell-type, which is due to characteristic expression of RNA-binding proteins, that influence TDP-43’s performance and define cell-type specific splicing. Among splicing events commonly dysregulated in both cell lines, we identify some that are TDP-43-dependent also in human cells. Inclusion levels of these alternative exons are altered in tissues of patients suffering from FTLD and IBM. We therefore propose that TDP-43 dysfunction contributes to disease development either in a common or a tissue-specific manner.</jats:p> 2023-01-31T18:27:46Z 2023-01-31T18:27:46Z 2022 2023-01-31T18:22:00Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147815 Fraenkel, Ernest. 2022. "Cell environment shapes TDP-43 function with implications in neuronal and muscle disease." Communications Biology, 5 (1). en 10.1038/S42003-022-03253-8 Communications Biology Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Fraenkel, Ernest Cell environment shapes TDP-43 function with implications in neuronal and muscle disease |
| title | Cell environment shapes TDP-43 function with implications in neuronal and muscle disease |
| title_full | Cell environment shapes TDP-43 function with implications in neuronal and muscle disease |
| title_fullStr | Cell environment shapes TDP-43 function with implications in neuronal and muscle disease |
| title_full_unstemmed | Cell environment shapes TDP-43 function with implications in neuronal and muscle disease |
| title_short | Cell environment shapes TDP-43 function with implications in neuronal and muscle disease |
| title_sort | cell environment shapes tdp 43 function with implications in neuronal and muscle disease |
| url | https://hdl.handle.net/1721.1/147815 |
| work_keys_str_mv | AT fraenkelernest cellenvironmentshapestdp43functionwithimplicationsinneuronalandmuscledisease |