hnRNP U enhances caspase-9 splicing and is modulated by AKT-dependent phosphorylation of hnRNP L
Vu, NT; Park, MA; Shultz, JC; Goehe, RW; Hoeferlin, LA; Shultz, MD; Smith, SA; Lynch, KW; Chalfant, CE
HERO ID
2901861
Reference Type
Journal Article
Year
2013
Language
English
PMID
| HERO ID | 2901861 |
|---|---|
| In Press | No |
| Year | 2013 |
| Title | hnRNP U enhances caspase-9 splicing and is modulated by AKT-dependent phosphorylation of hnRNP L |
| Authors | Vu, NT; Park, MA; Shultz, JC; Goehe, RW; Hoeferlin, LA; Shultz, MD; Smith, SA; Lynch, KW; Chalfant, CE |
| Journal | Journal of Biological Chemistry |
| Volume | 288 |
| Issue | 12 |
| Page Numbers | 8575-8584 |
| Abstract | Caspase-9 has two splice variants, pro-apoptotic caspase-9a and anti-apoptotic caspase-9b, which are regulated by RNA trans-factors associated with exon 3 of caspase-9 pre-mRNA (C9/E3). In this study, we identified hnRNP U as an RNA trans-factor associated with C9/E3. Down-regulation of hnRNP U led to a decrease in the caspase-9a/9b mRNA ratio, demonstrating a novel enhancing function. Importantly, hnRNP U bound specifically to C9/E3 at an RNA cis-element previously reported as the binding site for the splicing repressor, hnRNP L. Phosphorylated hnRNP L interfered with hnRNP U binding to C9/E3, and our results demonstrate the importance of the phosphoinositide 3-kinase/AKT pathway in modulating the association of hnRNP U to C9/E3. Taken together, these findings show that hnRNP U competes with hnRNP L for binding to C9/E3 to enhance the inclusion of the four-exon cassette, and this splice-enhancing function is blocked by the AKT pathway via phosphorylation of hnRNP L. |
| Doi | 10.1074/jbc.M112.443333 |
| Pmid | 23396972 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |