DataSets / Project home (Blencowe lab interactome profiling)
Blencowe lab interactome profiling
First Author: Thomas Gonatopoulos-Pournatzis; MS data from Jonathan Roth
Abstract:
   This project contains files associated with publications from the Blencowe lab.

Currently, the project contains all data associated with the following manuscript conditionally accepted at Molecular Cell :
Genome-wide CRISPR-Cas9 interrogation of splicing networks reveals a mechanism for recognition of autism-misregulated neuronal microexons

Alternative splicing is crucial for diverse cellular, developmental and pathological processes. However, the full networks of factors that control individual splicing events are not known. Here, we describe a CRISPR-based strategy for the genome-wide elucidation of pathways that control splicing, and apply it to microexons with important functions in nervous system development and that are commonly misregulated in autism. Approximately 200 genes associated with functionally diverse regulatory layers, and enriched in genetic links to autism, control neuronal microexons. Remarkably, the widely expressed RNA binding proteins Srsf11 and Rnps1 directly, preferentially and frequently co-activate these microexons. These factors form critical interactions with the neuronal splicing regulator Srrm4 and a bi-partite intronic splicing enhancer element to promote spliceosome formation. Our study thus presents a versatile system for the identification of entire splicing regulatory pathways, and further reveals a common mechanism for the definition of neuronal microexons that is disrupted in autism.

For details on the manuscript please contact Benjamin Blencowe (b.blencowe@utoronto.ca). For details on the proteomics datasets please contact Anne-Claude Gingras (gingras@lunenfeld.ca).


Navigating this website

• The data included here is by default filtered with BFDR ≤ 0.01, as calculated by SAINTexpress; unselect the "high confidence" buttons to view all data. You can also download a complete interactome table through the Supplementary data section (left).

Select "Explore baits" (left) to view all baits profiled, organized alphabetically (view as a list). Clicking on a bait will retrieve all its interactors (high confidence by default) and indicate which interactions are already deposited in the BioGRID and IntAct databases.

• Selecting multiple baits (or all baits) will enable a download of the SAINT result file that can be opened at ProHits-viz for visualization and further exploration.

• Also see the many links to excellent external resources for the baits and/or preys, including ProteinAtlas, ProteomicsDB, NCBI Gene, GeneCards and UniProt.

• Search for a bait or prey by Official Gene Symbol through the "Search" tab on left (or at the top). You will be able to search across all projects you have access to.

• Please see the Supplementary Data tab for additional figures, tables and input files for Cytoscape and prohits-viz.

Note that the mass spectrometry data has been deposited at MassIVE. The FLAG dataset has been assigned identifiers MSV000082174 and PXD009226 respectively. Likewise, the BioID dataset has been assigned IDs MSV000082169 and PXD009213.


Copyright © 2012 Gingras labs, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital.