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Combinatorial control of signal-induced exon repression by hnRNP L and PSF.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Melton, Alexis A. Jackson, Jason K. Wang, Jiarong Lynch, Kristen W. |
| Copyright Year | 2007 |
| Abstract | Cells can regulate their protein repertoire in response to extracellular stimuli via alternative splicing; however, the mechanisms controlling this process are poorly understood. The CD45 gene undergoes alternative splicing in response to T-cell activation to regulate T-cell function. The ESS1 splicing silencer in CD45 exon 4 confers basal exon skipping in resting T cells through the activity of hnRNP L and confers activation-induced exon skipping in T cells via previously unknown mechanisms. Here we have developed an in vitro splicing assay that recapitulates the signal-induced alternative splicing of CD45 and demonstrate that cellular stimulation leads to two changes to the ESS1-bound splicing regulatory complex. Activation-induced posttranslational modification of hnRNP L correlates with a modest increase in the protein's repressive activity. More importantly, the splicing factor PSF is recruited to the ESS1 complex in an activation-dependent manner and accounts for the majority of the signal-regulated ESS1 activity. The associations of hnRNP L and PSF with the ESS1 complex are largely independent of each other, but together these proteins account for the total signal-regulated change in CD45 splicing observed in vitro and in vivo. Such a combinatorial effect on splicing allows for precise regulation of signal-induced alternative splicing. |
| Starting Page | 49 |
| Ending Page | 54 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://mcb.asm.org/content/27/19/6972.full.pdf |
| Alternate Webpage(s) | http://www.med.upenn.edu/lynchlab/publications/07Meltonetal.pdf |
| PubMed reference number | 17664280v1 |
| Volume Number | 27 |
| Issue Number | 19 |
| Journal | Molecular and cellular biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Alternative Splicing Cell physiology Heterogeneous-Nuclear Ribonucleoprotein Group A-B Heterogeneous-Nuclear Ribonucleoprotein L Heterogeneous-Nuclear Ribonucleoproteins Interphase Cell Leukemia, B-Cell Mental association PTB-associated splicing factor Post-Translational Protein Processing RNA Splicing Repression, Psychology T-Lymphocyte |
| Content Type | Text |
| Resource Type | Article |
