 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 11, 2017 |
| Title |
Binding to SMN2 pre-mRNA-Protein complex elicits specificity for small molecule splicing modifiers |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Small molecule splicing modifiers have been extensively described which target the generic splicing machinery and thus have low target specificity. We have identified potent splicing modifiers with unprecedented high selectively, correcting the splicing deficit of the SMN2 (survival motor neuron 2) gene in Spinal Muscular Atrophy (SMA). Here we show that they directly bind to two sites of the SMN2 pre-mRNA, thereby stabilizing a novel ribonucleoprotein (RNP) complex in the SMN2 gene that is critical for the high target specificity of these small molecules over other genes. In addition to the therapeutic potential of these molecules for treatment of SMA, our work may have wide-ranging consequences for further research to identify small molecules that target splicing correction of specific genes by interacting with tertiary RNA structures.
|
| |
|
| Overall design |
mRNA profiling of type I SMA fibroblasts treated with NVS-SM1
|
| |
|
| Contributor(s) |
Sivaramakrishnan M, McCarthy K, Huber S, Campagne S, Meier S, Augustin A, Heckel T, Meistermann H, Hug M, Birrer P, Moursy A, Khawaja S, Giroud N, Golling S, Tzouros M, Banfai B, Duran-Pacheco G, Lamerz J, Hsiu Liu Y, Luebbers T, Ratni H, Clery A, Ebeling M, Paushkin S, Krainer AR, Allain F, Metzger F, Berntenis N, Schmucki R |
| Citation(s) |
29133793 |
| |
| Submission date |
Aug 24, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Roland Schmucki |
| E-mail(s) |
roland.schmucki@roche.com
|
| Organization name |
F. Hoffmann - La Roche AG
|
| Street address |
Grenzacherstrase
|
| City |
Basel |
| ZIP/Postal code |
4058 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA339972 |
| SRA |
SRP082685 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE86001_NVS-SM1_counts.gct.gz |
380.0 Kb |
(ftp)(http) |
GCT |
| GSE86001_NVS-SM1_junction_read_counts.txt.gz |
12.4 Mb |
(ftp)(http) |
TXT |
| GSE86001_NVS-SM1_nojunction_read_counts.txt.gz |
13.8 Mb |
(ftp)(http) |
TXT |
| GSE86001_NVS-SM1_read_counts.txt.gz |
14.4 Mb |
(ftp)(http) |
TXT |
| GSE86001_NVS-SM1_rpkms.gct.gz |
377.4 Kb |
(ftp)(http) |
GCT |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...