Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences far outpaces the research on the structure and functional interactions of these RNA gene sequences. We mine the evolutionary sequence record to derive precise information about the function and structure of RNAs and RNA-protein complexes. As in protein structure prediction, we use maximum entropy global probability models of sequence co-variation to infer evolutionarily constrained nucleotide-nucleotide interactions within RNA molecules and nucleotide-amino acid interactions in RNA-protein complexes. The predicted contacts allow all-atom blinded 3D structure prediction at good accuracy for several known RNA structures and RNA-protein complexes. For unknown structures, we predict contacts in 160 non-coding RNA families. Beyond 3D structure prediction, evolutionary couplings help identify important functional interactions?e.g., at switch points in riboswitches and at a complex nucleation site in HIV. Aided by increasing sequence accumulation, evolutionary coupling analysis can accelerate the discovery of functional interactions and 3D structures involving RNA.
%0 Journal Article
%1 Weinreb20163D
%A Weinreb, Caleb
%A Riesselman, Adam J.
%A Ingraham, John B.
%A Gross, Torsten
%A Sander, Chris
%A Marks, Debora S.
%D 2016
%I Elsevier
%J Cell
%K prediction rna structure
%N 4
%P 963--975
%R 10.1016/j.cell.2016.03.030
%T 3D RNA and Functional Interactions from Evolutionary Couplings
%U http://dx.doi.org/10.1016/j.cell.2016.03.030
%V 165
%X Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences far outpaces the research on the structure and functional interactions of these RNA gene sequences. We mine the evolutionary sequence record to derive precise information about the function and structure of RNAs and RNA-protein complexes. As in protein structure prediction, we use maximum entropy global probability models of sequence co-variation to infer evolutionarily constrained nucleotide-nucleotide interactions within RNA molecules and nucleotide-amino acid interactions in RNA-protein complexes. The predicted contacts allow all-atom blinded 3D structure prediction at good accuracy for several known RNA structures and RNA-protein complexes. For unknown structures, we predict contacts in 160 non-coding RNA families. Beyond 3D structure prediction, evolutionary couplings help identify important functional interactions?e.g., at switch points in riboswitches and at a complex nucleation site in HIV. Aided by increasing sequence accumulation, evolutionary coupling analysis can accelerate the discovery of functional interactions and 3D structures involving RNA.
@article{Weinreb20163D,
abstract = {Non-coding {RNAs} are ubiquitous, but the discovery of new {RNA} gene sequences far outpaces the research on the structure and functional interactions of these {RNA} gene sequences. We mine the evolutionary sequence record to derive precise information about the function and structure of {RNAs} and {RNA}-protein complexes. As in protein structure prediction, we use maximum entropy global probability models of sequence co-variation to infer evolutionarily constrained nucleotide-nucleotide interactions within {RNA} molecules and nucleotide-amino acid interactions in {RNA}-protein complexes. The predicted contacts allow all-atom blinded {3D} structure prediction at good accuracy for several known {RNA} structures and {RNA}-protein complexes. For unknown structures, we predict contacts in 160 non-coding {RNA} families. Beyond {3D} structure prediction, evolutionary couplings help identify important functional interactions?e.g., at switch points in riboswitches and at a complex nucleation site in {HIV}. Aided by increasing sequence accumulation, evolutionary coupling analysis can accelerate the discovery of functional interactions and {3D} structures involving {RNA}.},
added-at = {2018-12-02T16:09:07.000+0100},
author = {Weinreb, Caleb and Riesselman, Adam J. and Ingraham, John B. and Gross, Torsten and Sander, Chris and Marks, Debora S.},
biburl = {https://www.bibsonomy.org/bibtex/2d1f4c41a80707fc3ce07c9079ab10c87/karthikraman},
citeulike-article-id = {14015598},
citeulike-linkout-0 = {http://www.cell.com/cell/abstract/S0092-8674(16)30328-2},
citeulike-linkout-1 = {http://dx.doi.org/10.1016/j.cell.2016.03.030},
day = 31,
doi = {10.1016/j.cell.2016.03.030},
interhash = {99d978b6d327cd7742b1a24cdae4ecb6},
intrahash = {d1f4c41a80707fc3ce07c9079ab10c87},
issn = {00928674},
journal = {Cell},
keywords = {prediction rna structure},
month = may,
number = 4,
pages = {963--975},
posted-at = {2016-05-31 17:22:10},
priority = {2},
publisher = {Elsevier},
timestamp = {2018-12-02T16:09:07.000+0100},
title = {{3D} {RNA} and Functional Interactions from Evolutionary Couplings},
url = {http://dx.doi.org/10.1016/j.cell.2016.03.030},
volume = 165,
year = 2016
}