The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation
The RNA-binding proteins PTBP1 and PTBP2 control programs of alternative splicing during neuronal development. PTBP2 was found to maintain embryonic splicing patterns of many synaptic and cytoskeletal proteins during differentiation of neuronal progenitor cells (NPCs) into early neurons. However, th...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/09268 |
| _version_ | 1811227427547906048 |
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| author | Anthony J Linares Chia-Ho Lin Andrey Damianov Katrina L Adams Bennett G Novitch Douglas L Black |
| author_facet | Anthony J Linares Chia-Ho Lin Andrey Damianov Katrina L Adams Bennett G Novitch Douglas L Black |
| author_sort | Anthony J Linares |
| collection | DOAJ |
| description | The RNA-binding proteins PTBP1 and PTBP2 control programs of alternative splicing during neuronal development. PTBP2 was found to maintain embryonic splicing patterns of many synaptic and cytoskeletal proteins during differentiation of neuronal progenitor cells (NPCs) into early neurons. However, the role of the earlier PTBP1 program in embryonic stem cells (ESCs) and NPCs was not clear. We show that PTBP1 controls a program of neuronal gene expression that includes the transcription factor Pbx1. We identify exons specifically regulated by PTBP1 and not PTBP2 as mouse ESCs differentiate into NPCs. We find that PTBP1 represses Pbx1 exon 7 and the expression of the neuronal Pbx1a isoform in ESCs. Using CRISPR-Cas9 to delete regulatory elements for exon 7, we induce Pbx1a expression in ESCs, finding that this activates transcription of neuronal genes. Thus, PTBP1 controls the activity of Pbx1 to suppress its neuronal transcriptional program prior to induction of NPC development. |
| first_indexed | 2024-04-12T09:42:20Z |
| format | Article |
| id | doaj.art-6e06fcc18c114fd49ebf33b7f6580d31 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:42:20Z |
| publishDate | 2015-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6e06fcc18c114fd49ebf33b7f6580d312022-12-22T03:38:03ZengeLife Sciences Publications LtdeLife2050-084X2015-12-01410.7554/eLife.09268The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiationAnthony J Linares0https://orcid.org/0000-0002-2484-7252Chia-Ho Lin1Andrey Damianov2Katrina L Adams3Bennett G Novitch4Douglas L Black5https://orcid.org/0000-0002-2705-8187Molecular Biology Institute Graduate Program, University of California, Los Angeles, Los Angeles, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United StatesMolecular Biology Institute Graduate Program, University of California, Los Angeles, Los Angeles, United States; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesThe RNA-binding proteins PTBP1 and PTBP2 control programs of alternative splicing during neuronal development. PTBP2 was found to maintain embryonic splicing patterns of many synaptic and cytoskeletal proteins during differentiation of neuronal progenitor cells (NPCs) into early neurons. However, the role of the earlier PTBP1 program in embryonic stem cells (ESCs) and NPCs was not clear. We show that PTBP1 controls a program of neuronal gene expression that includes the transcription factor Pbx1. We identify exons specifically regulated by PTBP1 and not PTBP2 as mouse ESCs differentiate into NPCs. We find that PTBP1 represses Pbx1 exon 7 and the expression of the neuronal Pbx1a isoform in ESCs. Using CRISPR-Cas9 to delete regulatory elements for exon 7, we induce Pbx1a expression in ESCs, finding that this activates transcription of neuronal genes. Thus, PTBP1 controls the activity of Pbx1 to suppress its neuronal transcriptional program prior to induction of NPC development.https://elifesciences.org/articles/09268alternative splicingRNA binding proteinembryonic stem cellsposttranscriptional regulation |
| spellingShingle | Anthony J Linares Chia-Ho Lin Andrey Damianov Katrina L Adams Bennett G Novitch Douglas L Black The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation eLife alternative splicing RNA binding protein embryonic stem cells posttranscriptional regulation |
| title | The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation |
| title_full | The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation |
| title_fullStr | The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation |
| title_full_unstemmed | The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation |
| title_short | The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation |
| title_sort | splicing regulator ptbp1 controls the activity of the transcription factor pbx1 during neuronal differentiation |
| topic | alternative splicing RNA binding protein embryonic stem cells posttranscriptional regulation |
| url | https://elifesciences.org/articles/09268 |
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