| RRC ID |
45535
|
| 著者 |
Chen F, Zhou Y, Qi YB, Khivansara V, Li H, Chun SY, Kim JK, Fu XD, Jin Y.
|
| タイトル |
Context-dependent modulation of Pol II CTD phosphatase SSUP-72 regulates alternative polyadenylation in neuronal development.
|
| ジャーナル |
Genes Dev
|
| Abstract |
Alternative polyadenylation (APA) is widespread in neuronal development and activity-mediated neural plasticity. However, the underlying molecular mechanisms are largely unknown. We used systematic genetic studies and genome-wide surveys of the transcriptional landscape to identify a context-dependent regulatory pathway controlling APA in the Caenorhabditis elegans nervous system. Loss of function in ssup-72, a Ser5 phosphatase for the RNA polymerase II (Pol II) C-terminal domain (CTD), dampens transcription termination at a strong intronic polyadenylation site (PAS) in unc-44/ankyrin yet promotes termination at the weak intronic PAS of the MAP kinase dlk-1. A nuclear protein, SYDN-1, which regulates neuronal development, antagonizes the function of SSUP-72 and several nuclear polyadenylation factors. This regulatory pathway allows the production of a neuron-specific isoform of unc-44 and an inhibitory isoform of dlk-1. Dysregulation of the unc-44 and dlk-1 mRNA isoforms in sydn-1 mutants impairs neuronal development. Deleting the intronic PAS of unc-44 results in increased pre-mRNA processing of neuronal ankyrin and suppresses sydn-1 mutants. These results reveal a mechanism by which regulation of CTD phosphorylation controls coding region APA in the nervous system.
|
| 巻・号 |
29(22)
|
| ページ |
2377-90
|
| 公開日 |
2015-11-15
|
| DOI |
10.1101/gad.266650.115
|
| PII |
29/22/2377
|
| PMID |
26588990
|
| PMC |
PMC4691892
|
| MeSH |
Animals
Ankyrins / genetics
Ankyrins / metabolism
Caenorhabditis elegans / enzymology*
Caenorhabditis elegans / genetics
Caenorhabditis elegans / growth & development*
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Gene Expression Regulation, Developmental
MAP Kinase Kinase Kinases / genetics
MAP Kinase Kinase Kinases / metabolism
Mutation
Neurons / enzymology
Phosphoprotein Phosphatases / genetics
Phosphoprotein Phosphatases / metabolism*
Polyadenylation
Protein Binding
|
| IF |
9.527
|
| 引用数 |
4
|
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
GENETICS & HEREDITY
CELL BIOLOGY
|
| リソース情報 |
| 線虫 |
tm2304
tm349
tm2715
tm2802
tm2657
tm4024 |
