|
| Status |
Public on Oct 22, 2019 |
| Title |
miR200 family target gene identification in Neuro2A cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Rett syndrome is a complex neurodevelopmental disorder that is mainly caused by mutations in MECP2. However, mutations in FOXG1 cause a less frequent non-congenital form called atypical Rett syndrome. FOXG1 is a key transcription factor implicated in forebrain development, where it maintains the balance between progenitor proliferation and neuronal differentiation. Using quantitative proteomics and genome-wide small RNA sequencing, we identified that FOXG1 interacts with the ATP-dependent RNA helicase, DDX5/p68 and controls the biogenesis of miRNAs. Both, FOXG1 and DDX5 bind to the miR200b/a/429 primary transcript and associate with the microprocessor complex, whereby DDX5 recruits FOXG1 to DROSHA. In vivo and in vitro experiments show that both FOXG1 and DDX5 are necessary for effective maturation of miR200b/a/429. RNAseq analyses of Foxg1-heterozygote hippocampi and miR200b/a/429 overexpressing Neuro-2a cells revealed that the cAMP-dependent protein kinase type II-beta regulatory subunit (PRKAR2B) is a target of miR200 in neural cells. Since it is known that PRKAR2B inhibits postsynaptic functions by attenuating protein kinase A (PKA) activity, increased PRKAR2B levels may contribute to neuronal dysfunctions in FOXG1 Rett syndrome.
|
| |
|
| Overall design |
miR200 family members were overexpressed in Neuro2A cells to identify target genes for miR200 family members. As a control a sponge for miR200 family members was transfected in Neuro2A cells. 2 replicates of miR200 family overexpression were compared to 3 replicates of sponge transfected samples. miR200 overexpression was verified by RT-qPCR
|
| |
|
| Contributor(s) |
Weise SC, Arumugam G, Vogel T, Videm P, Backofen R, Fischer A, Sananbenesi F |
| Citation(s) |
30539330 |
| BioProject |
PRJNA417965 |
| |
| Submission date |
Nov 13, 2017 |
| Last update date |
Oct 22, 2019 |
| Contact name |
Tanja Vogel |
| E-mail(s) |
tanja.vogel@anat.uni-freiburg.de
|
| Phone |
497612035086
|
| Organization name |
University of Freiburg
|
| Department |
Institute for Anatomy and Cell Biology
|
| Lab |
Molecular Embryology
|
| Street address |
Albertstr. 17
|
| City |
Freiburg |
| ZIP/Postal code |
79104 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (5)
|
|
| Relations |
| SRA |
SRP124784 |
Less...
More...