TY - JOUR
T1 - SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes
AU - Brannan, Kristopher W.
AU - Jin, Wenhao
AU - Huelga, Stephanie C.
AU - Banks, Charles A.S.
AU - Gilmore, Joshua M.
AU - Florens, Laurence
AU - Washburn, Michael P.
AU - Van Nostrand, Eric L.
AU - Pratt, Gabriel A.
AU - Schwinn, Marie K.
AU - Daniels, Danette L.
AU - Yeo, Gene W.
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/10/20
Y1 - 2016/10/20
N2 - RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs. This motivated SONAR, a computational approach that predicts RNA binding activity by analyzing large-scale affinity precipitation-MS protein-protein interactomes. Without relying on sequence or structure information, SONAR identifies 1,923 human, 489 fly, and 745 yeast RBPs, including over 100 human candidate RBPs that contain zinc finger domains. Enhanced CLIP confirms RNA binding activity and identifies transcriptome-wide RNA binding sites for SONAR-predicted RBPs, revealing unexpected RNA binding activity for disease-relevant proteins and DNA binding proteins.
AB - RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs. This motivated SONAR, a computational approach that predicts RNA binding activity by analyzing large-scale affinity precipitation-MS protein-protein interactomes. Without relying on sequence or structure information, SONAR identifies 1,923 human, 489 fly, and 745 yeast RBPs, including over 100 human candidate RBPs that contain zinc finger domains. Enhanced CLIP confirms RNA binding activity and identifies transcriptome-wide RNA binding sites for SONAR-predicted RBPs, revealing unexpected RNA binding activity for disease-relevant proteins and DNA binding proteins.
KW - RNA-binding proteins
KW - machine-learning
KW - protein-protein interaction networks
KW - support vector machine
UR - http://www.scopus.com/inward/record.url?scp=84992157070&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992157070&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2016.09.003
DO - 10.1016/j.molcel.2016.09.003
M3 - Article
C2 - 27720645
AN - SCOPUS:84992157070
SN - 1097-2765
VL - 64
SP - 282
EP - 293
JO - Molecular Cell
JF - Molecular Cell
IS - 2
ER -