Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factors
Single-cell transcriptomes are established by transcription factors (TFs), which determine a cell's gene-expression complement. Post-transcriptional regulation of single-cell transcriptomes, and the RNA binding proteins (RBPs) responsible, are more technically challenging to determine, and comb...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2019-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/46726 |
| _version_ | 1811253011386728448 |
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| author | Morgan Thompson Ryan Bixby Robert Dalton Alexa Vandenburg John A Calarco Adam D Norris |
| author_facet | Morgan Thompson Ryan Bixby Robert Dalton Alexa Vandenburg John A Calarco Adam D Norris |
| author_sort | Morgan Thompson |
| collection | DOAJ |
| description | Single-cell transcriptomes are established by transcription factors (TFs), which determine a cell's gene-expression complement. Post-transcriptional regulation of single-cell transcriptomes, and the RNA binding proteins (RBPs) responsible, are more technically challenging to determine, and combinatorial TF-RBP coordination of single-cell transcriptomes remains unexplored. We used fluorescent reporters to visualize alternative splicing in single Caenorhabditis elegans neurons, identifying complex splicing patterns in the neuronal kinase sad-1. Most neurons express both isoforms, but the ALM mechanosensory neuron expresses only the exon-included isoform, while its developmental sister cell the BDU neuron expresses only the exon-skipped isoform. A cascade of three cell-specific TFs and two RBPs are combinatorially required for sad-1 exon inclusion. Mechanistically, TFs combinatorially ensure expression of RBPs, which interact with sad-1 pre-mRNA. Thus a combinatorial TF-RBP code controls single-neuron sad-1 splicing. Additionally, we find ‘phenotypic convergence,’ previously observed for TFs, also applies to RBPs: different RBP combinations generate similar splicing outcomes in different neurons. |
| first_indexed | 2024-04-12T16:43:18Z |
| format | Article |
| id | doaj.art-693d9901788f4ee597a4c972cb15372c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:43:18Z |
| publishDate | 2019-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-693d9901788f4ee597a4c972cb15372c2022-12-22T03:24:40ZengeLife Sciences Publications LtdeLife2050-084X2019-07-01810.7554/eLife.46726Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factorsMorgan Thompson0Ryan Bixby1Robert Dalton2Alexa Vandenburg3John A Calarco4https://orcid.org/0000-0002-2197-7801Adam D Norris5https://orcid.org/0000-0002-0570-7414Biological Sciences, Southern Methodist University, Dallas, United StatesBiological Sciences, Southern Methodist University, Dallas, United StatesBiological Sciences, Southern Methodist University, Dallas, United StatesBiological Sciences, Southern Methodist University, Dallas, United StatesCell & Systems Biology, University of Toronto, Toronto, CanadaBiological Sciences, Southern Methodist University, Dallas, United StatesSingle-cell transcriptomes are established by transcription factors (TFs), which determine a cell's gene-expression complement. Post-transcriptional regulation of single-cell transcriptomes, and the RNA binding proteins (RBPs) responsible, are more technically challenging to determine, and combinatorial TF-RBP coordination of single-cell transcriptomes remains unexplored. We used fluorescent reporters to visualize alternative splicing in single Caenorhabditis elegans neurons, identifying complex splicing patterns in the neuronal kinase sad-1. Most neurons express both isoforms, but the ALM mechanosensory neuron expresses only the exon-included isoform, while its developmental sister cell the BDU neuron expresses only the exon-skipped isoform. A cascade of three cell-specific TFs and two RBPs are combinatorially required for sad-1 exon inclusion. Mechanistically, TFs combinatorially ensure expression of RBPs, which interact with sad-1 pre-mRNA. Thus a combinatorial TF-RBP code controls single-neuron sad-1 splicing. Additionally, we find ‘phenotypic convergence,’ previously observed for TFs, also applies to RBPs: different RBP combinations generate similar splicing outcomes in different neurons.https://elifesciences.org/articles/46726RNAsplicingsingle neuron |
| spellingShingle | Morgan Thompson Ryan Bixby Robert Dalton Alexa Vandenburg John A Calarco Adam D Norris Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factors eLife RNA splicing single neuron |
| title | Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factors |
| title_full | Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factors |
| title_fullStr | Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factors |
| title_full_unstemmed | Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factors |
| title_short | Splicing in a single neuron is coordinately controlled by RNA binding proteins and transcription factors |
| title_sort | splicing in a single neuron is coordinately controlled by rna binding proteins and transcription factors |
| topic | RNA splicing single neuron |
| url | https://elifesciences.org/articles/46726 |
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