Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Differential transcript stability measurements in MDA-MB-231 vs. MDA-LM2 cells

ABSTRACT: We performed whole-genome stability measurements for MDA-MB-231 and its highly metastatic derivative MDA-LM2. Our goal was to identify post-transcriptonal regulons that are deregulated en route to higher metastatic capacity. Cells were pulsed with 4-thiouridine for 2 hours and then RNA was extracted at 0, 2, 4, and 7 hr time-points in quadruplicate from each cell line. 4sU labeling followed by RNA-seq was then used to measure the abundance of transcripts in each population. A decay rate was estimated based on the rate at which transcript abundance was reduced at these time-points.

ORGANISM(S): Homo sapiens

SUBMITTER: Hani Goodarzi

PROVIDER: E-GEOD-49608 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins.

Goodarzi Hani H Zhang Steven S Buss Colin G CG Fish Lisa L Tavazoie Saeed S Tavazoie Sohail F SF

Nature 20140709 7517

Aberrant regulation of RNA stability has an important role in many disease states. Deregulated post-transcriptional modulation, such as that governed by microRNAs targeting linear sequence elements in messenger RNAs, has been implicated in the progression of many cancer types. A defining feature of RNA is its ability to fold into structures. However, the roles of structural mRNA elements in cancer progression remain unexplored. Here we performed an unbiased search for post-transcriptional modula ...[more]

PMID: 25043050

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Project description: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 following subset Series: 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 Refer to individual Series

Dataset Information

Differential transcript stability measurements in MDA-MB-231 vs. MDA-LM2 cells

Publications

Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins.

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