|
| Status |
Public on Feb 28, 2012 |
| Title |
Systematic Discovery of Structural Elements Governing Mammalian mRNA Stability |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
Decoding post-transcriptional regulatory programs underlying gene expression is a crucial step toward a predictive dynamical understanding of cellular state transitions. Despite recent systematic efforts, the sequence determinants of such mechanisms remain largely uncharacterized. An important obstacle in revealing these elements stems from the contribution of local secondary structures in defining interaction partners in a variety of regulatory contexts, including but not limited to transcript stability, alternative splicing and localization. There are many documented instances where the presence of a structural regulatory element dictates alternative splicing patterns (e.g. human cardiac troponin T) or affects other aspects of RNA biology. Thus, a full characterization of post-transcriptional regulatory programs requires capturing information provided by both local secondary structures and the underlying sequence. We have developed a computational framework based on context-free grammars and mutual information that systematically explores the immense space of structural elements and reveals motifs that are significantly informative of genome-wide measurements of RNA behavior. The application of this framework to genome-wide mammalian mRNA stability data revealed eight highly significant elements with substantial structural information, for the strongest of which we showed a major role in global mRNA regulation. Through biochemistry, mass-spectrometry, and in vivo binding studies, we identified HNRPA2B1 as the key regulator that binds this element and stabilizes a large number of its target genes. Ultimately, we created a global post-transcriptional regulatory map based on the identity of the discovered linear and structural cis-regulatory elements, their regulatory interactions and their target pathways. This approach can also be employed to reveal the structural elements that modulate other aspects of RNA behavior.
This SuperSeries is composed of the SubSeries listed below.
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| |
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| Overall design |
Refer to individual Series
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| |
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| Citation(s) |
22495308 |
| |
| Submission date |
Feb 14, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Hani Goodarzi |
| Organization name |
UCSF
|
| Department |
Biochemistry and Biophysics
|
| Street address |
600 16th St, GH S312D
|
| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
|
| Samples (43)
|
|
| This SuperSeries is composed of the following SubSeries:
|
| GSE35749 |
sRSM1 synthetic decoy vs. scrambled transfections in MDA-MB-231 cells |
| GSE35753 |
HNRPA2B1 RIP-chip |
| GSE35756 |
Whole-genome decay rate measurements in MDA-MB-231 cells transfected with HNRPA2B1 siRNAs versus controls |
| GSE35757 |
siRNA-mediated HNRPA2B1 knock-down in MDA-MB-231 cells |
| GSE35799 |
HNRPA2B1 HITS-CLIP |
|
| Relations |
| BioProject |
PRJNA152199 |
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