RAG-3D: A search tool for RNA 3D substructures
Abstract
In this study, to address many challenges in RNA structure/function prediction, the characterization of RNA's modular architectural units is required. Using the RNA-As-Graphs (RAG) database, we have previously explored the existence of secondary structure (2D) submotifs within larger RNA structures. Here we present RAG-3D—a dataset of RNA tertiary (3D) structures and substructures plus a web-based search tool—designed to exploit graph representations of RNAs for the goal of searching for similar 3D structural fragments. The objects in RAG-3D consist of 3D structures translated into 3D graphs, cataloged based on the connectivity between their secondary structure elements. Each graph is additionally described in terms of its subgraph building blocks. The RAG-3D search tool then compares a query RNA 3D structure to those in the database to obtain structurally similar structures and substructures. This comparison reveals conserved 3D RNA features and thus may suggest functional connections. Though RNA search programs based on similarity in sequence, 2D, and/or 3D structural elements are available, our graph-based search tool may be advantageous for illuminating similarities that are not obvious; using motifs rather than sequence space also reduces search times considerably. Ultimately, such substructuring could be useful for RNA 3D structure prediction, structure/function inference and inverse folding.
- Authors:
-
- New York City College of Technology, City Univ. of New York, Brooklyn, NY (United States)
- New York Univ., New York, NY (United States)
- Publication Date:
- Research Org.:
- New York Univ. (NYU), NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1239896
- Grant/Contract Number:
- AC02-98CH10886
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nucleic Acids Research
- Additional Journal Information:
- Journal Volume: 43; Journal Issue: 19; Journal ID: ISSN 0305-1048
- Publisher:
- Oxford University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Zahran, Mai, Sevim Bayrak, Cigdem, Elmetwaly, Shereef, and Schlick, Tamar. RAG-3D: A search tool for RNA 3D substructures. United States: N. p., 2015.
Web. doi:10.1093/nar/gkv823.
Zahran, Mai, Sevim Bayrak, Cigdem, Elmetwaly, Shereef, & Schlick, Tamar. RAG-3D: A search tool for RNA 3D substructures. United States. https://doi.org/10.1093/nar/gkv823
Zahran, Mai, Sevim Bayrak, Cigdem, Elmetwaly, Shereef, and Schlick, Tamar. Mon .
"RAG-3D: A search tool for RNA 3D substructures". United States. https://doi.org/10.1093/nar/gkv823. https://www.osti.gov/servlets/purl/1239896.
@article{osti_1239896,
title = {RAG-3D: A search tool for RNA 3D substructures},
author = {Zahran, Mai and Sevim Bayrak, Cigdem and Elmetwaly, Shereef and Schlick, Tamar},
abstractNote = {In this study, to address many challenges in RNA structure/function prediction, the characterization of RNA's modular architectural units is required. Using the RNA-As-Graphs (RAG) database, we have previously explored the existence of secondary structure (2D) submotifs within larger RNA structures. Here we present RAG-3D—a dataset of RNA tertiary (3D) structures and substructures plus a web-based search tool—designed to exploit graph representations of RNAs for the goal of searching for similar 3D structural fragments. The objects in RAG-3D consist of 3D structures translated into 3D graphs, cataloged based on the connectivity between their secondary structure elements. Each graph is additionally described in terms of its subgraph building blocks. The RAG-3D search tool then compares a query RNA 3D structure to those in the database to obtain structurally similar structures and substructures. This comparison reveals conserved 3D RNA features and thus may suggest functional connections. Though RNA search programs based on similarity in sequence, 2D, and/or 3D structural elements are available, our graph-based search tool may be advantageous for illuminating similarities that are not obvious; using motifs rather than sequence space also reduces search times considerably. Ultimately, such substructuring could be useful for RNA 3D structure prediction, structure/function inference and inverse folding.},
doi = {10.1093/nar/gkv823},
journal = {Nucleic Acids Research},
number = 19,
volume = 43,
place = {United States},
year = {Mon Aug 24 00:00:00 EDT 2015},
month = {Mon Aug 24 00:00:00 EDT 2015}
}
Web of Science
Works referenced in this record:
Revealing the world of RNA interference
journal, September 2004
- Mello, Craig C.; Conte, Darryl
- Nature, Vol. 431, Issue 7006
fRNAdb: a platform for mining/annotating functional RNA candidates from non-coding RNA sequences
journal, January 2007
- Kin, T.; Yamada, K.; Terai, G.
- Nucleic Acids Research, Vol. 35, Issue Database
The kink-turn: a new RNA secondary structure motif
journal, August 2001
- Klein, D. J.
- The EMBO Journal, Vol. 20, Issue 15
Predicting Helical Topologies in RNA Junctions as Tree Graphs
journal, August 2013
- Laing, Christian; Jung, Segun; Kim, Namhee
- PLoS ONE, Vol. 8, Issue 8
Non–coding RNA genes and the modern RNA world
journal, December 2001
- Eddy, Sean R.
- Nature Reviews Genetics, Vol. 2, Issue 12
The Sarcin/Ricin Loop, a Modular RNA
journal, March 1995
- Szewczak, A. A.; Moore, P. B.
- Journal of Molecular Biology, Vol. 247, Issue 1
The ARTS web server for aligning RNA tertiary structures
journal, July 2006
- Dror, O.; Nussinov, R.; Wolfson, H. J.
- Nucleic Acids Research, Vol. 34, Issue Web Server
SARA: a server for function annotation of RNA structures
journal, May 2009
- Capriotti, E.; Marti-Renom, M. A.
- Nucleic Acids Research, Vol. 37, Issue Web Server
R3D-BLAST: a search tool for similar RNA 3D substructures
journal, May 2011
- Liu, Y. -C.; Yang, C. -H.; Chen, K. -T.
- Nucleic Acids Research, Vol. 39, Issue suppl
Long noncoding RNAs and the genetics of cancer
journal, May 2013
- Cheetham, S. W.; Gruhl, F.; Mattick, J. S.
- British Journal of Cancer, Vol. 108, Issue 12
On the occurrence of the T-loop RNA folding motif in large RNA molecules
journal, June 2003
- Krasilnikov, A. S.
- RNA, Vol. 9, Issue 6
RAG: RNA-As-Graphs database--concepts, analysis, and features
journal, February 2004
- Gan, H. H.; Fera, D.; Zorn, J.
- Bioinformatics, Vol. 20, Issue 8
RAG: An update to the RNA-As-Graphs resource
journal, January 2011
- Izzo, Joseph A.; Kim, Namhee; Elmetwaly, Shereef
- BMC Bioinformatics, Vol. 12, Issue 1
Non-coding RNAs in human disease
journal, November 2011
- Esteller, Manel
- Nature Reviews Genetics, Vol. 12, Issue 12
INFO-RNA—a server for fast inverse RNA folding satisfying sequence constraints
journal, July 2007
- Busch, Anke; Backofen, Rolf
- Nucleic Acids Research, Vol. 35, Issue suppl_2
RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures
journal, January 2010
- Popenda, Mariusz; Szachniuk, Marta; Blazewicz, Marek
- BMC Bioinformatics, Vol. 11, Issue 1
NASSAM: a server to search for and annotate tertiary interactions and motifs in three-dimensional structures of complex RNA molecules
journal, May 2012
- Hamdani, H. Y.; Appasamy, S. D.; Willett, P.
- Nucleic Acids Research, Vol. 40, Issue W1
Computational approaches to 3D modeling of RNA
journal, June 2010
- Laing, Christian; Schlick, Tamar
- Journal of Physics: Condensed Matter, Vol. 22, Issue 28
Computational Prediction of Riboswitch Tertiary Structures Including Pseudoknots by RAGTOP: A Hierarchical Graph Sampling Approach
book, January 2015
- Kim, Namhee; Zahran, Mai; Schlick, Tamar
- Methods in Enzymology
RNA Bricks—a database of RNA 3D motifs and their interactions
journal, November 2013
- Chojnowski, Grzegorz; Waleń, Tomasz; Bujnicki, Janusz M.
- Nucleic Acids Research, Vol. 42, Issue D1
From knotted to nested RNA structures: A variety of computational methods for pseudoknot removal
journal, January 2008
- Smit, S.; Rother, K.; Heringa, J.
- RNA, Vol. 14, Issue 3
VARNA: Interactive drawing and editing of the RNA secondary structure
journal, April 2009
- Darty, Kévin; Denise, Alain; Ponty, Yann
- Bioinformatics, Vol. 25, Issue 15
Frnakenstein: multiple target inverse RNA folding
journal, January 2012
- Lyngsø, Rune B.; Anderson, James WJ; Sizikova, Elena
- BMC Bioinformatics, Vol. 13, Issue 1
Exploring the repertoire of RNA secondary motifs using graph theory; implications for RNA design
journal, June 2003
- Gan, H. H.
- Nucleic Acids Research, Vol. 31, Issue 11
Modular RNA architecture revealed by computational analysis of existing pseudoknots and ribosomal RNAs
journal, February 2005
- Pasquali, S.
- Nucleic Acids Research, Vol. 33, Issue 4
The tmRNA Website: invasion by an intron
journal, January 2002
- Williams, K. P.
- Nucleic Acids Research, Vol. 30, Issue 1
RNA FRABASE version 1.0: an engine with a database to search for the three-dimensional fragments within RNA structures
journal, October 2007
- Popenda, Mariusz; Błażewicz, Marek; Szachniuk, Marta
- Nucleic Acids Research, Vol. 36, Issue suppl_1
Analysis and classification of RNA tertiary structures
journal, September 2008
- Abraham, M.; Dror, O.; Nussinov, R.
- RNA, Vol. 14, Issue 11
RAG: RNA-As-Graphs web resource
journal, January 2004
- Fera, Daniela; Kim, Namhee; Shiffeldrim, Nahum
- BMC Bioinformatics, Vol. 5, Issue 1, p. 88
FASTR3D: a fast and accurate search tool for similar RNA 3D structures
journal, May 2009
- Lai, C. -E.; Tsai, M. -Y.; Liu, Y. -C.
- Nucleic Acids Research, Vol. 37, Issue Web Server
How RNA folds
journal, October 1999
- Tinoco, Ignacio; Bustamante, Carlos
- Journal of Molecular Biology, Vol. 293, Issue 2
RNAiFOLD: A CONSTRAINT PROGRAMMING ALGORITHM FOR RNA INVERSE FOLDING AND MOLECULAR DESIGN
journal, April 2013
- Garcia-Martin, Juan Antonio; Clote, Peter; Dotu, Ivan
- Journal of Bioinformatics and Computational Biology, Vol. 11, Issue 02
Long non-coding RNAs: insights into functions
journal, March 2009
- Mercer, Tim R.; Dinger, Marcel E.; Mattick, John S.
- Nature Reviews Genetics, Vol. 10, Issue 3
Candidates for Novel RNA Topologies
journal, August 2004
- Kim, Namhee; Shiffeldrim, Nahum; Gan, Hin Hark
- Journal of Molecular Biology, Vol. 341, Issue 5
Ribo-gnome: The Big World of Small RNAs
journal, September 2005
- Zamore, P. D.
- Science, Vol. 309, Issue 5740
Graph-based sampling for approximating global helical topologies of RNA
journal, March 2014
- Kim, N.; Laing, C.; Elmetwaly, S.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 11
A modular strategy for generating starting conformations and data structures of polynucleotide helices for potential energy calculations
journal, December 1988
- Schlick, Tamar
- Journal of Computational Chemistry, Vol. 9, Issue 8
Graph Applications to RNA Structure and Function
book, October 2012
- Kim, Namhee; Fuhr, Katherine Niccole; Schlick, Tamar
- Biophysics of RNA Folding
Non-coding RNAs in the nervous system: Non-coding RNA in the nervous system
journal, August 2006
- Mehler, Mark F.; Mattick, John S.
- The Journal of Physiology, Vol. 575, Issue 2
Non-coding RNA
journal, April 2006
- Mattick, John S.; Makunin, Igor V.
- Human Molecular Genetics, Vol. 15, Issue suppl_1
miRBase: tools for microRNA genomics
journal, December 2007
- Griffiths-Jones, S.; Saini, H. K.; van Dongen, S.
- Nucleic Acids Research, Vol. 36, Issue Database
WebFR3D--a server for finding, aligning and analyzing recurrent RNA 3D motifs
journal, April 2011
- Petrov, A. I.; Zirbel, C. L.; Leontis, N. B.
- Nucleic Acids Research, Vol. 39, Issue suppl
Noncoding RNAs in cancer and cancer stem cells
journal, November 2013
- Huang, Tianzhi; Alvarez, Angel; Hu, Bo
- Chinese Journal of Cancer, Vol. 32, Issue 11
INFO-RNA--a fast approach to inverse RNA folding
journal, May 2006
- Busch, A.; Backofen, R.
- Bioinformatics, Vol. 22, Issue 15
The Protein Data Bank
journal, May 2002
- Berman, Helen M.; Battistuz, Tammy; Bhat, T. N.
- Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 6
NONCODE v2.0: decoding the non-coding
journal, December 2007
- He, S.; Liu, C.; Skogerbo, G.
- Nucleic Acids Research, Vol. 36, Issue Database
The building blocks and motifs of RNA architecture
journal, June 2006
- Leontis, Neocles B.; Lescoute, Aurelie; Westhof, Eric
- Current Opinion in Structural Biology, Vol. 16, Issue 3
Tools for the automatic identification and classification of RNA base pairs
journal, July 2003
- Yang, H.
- Nucleic Acids Research, Vol. 31, Issue 13
Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas
journal, August 2013
- Petrov, A. I.; Zirbel, C. L.; Leontis, N. B.
- RNA, Vol. 19, Issue 10
ARTS: alignment of RNA tertiary structures
journal, September 2005
- Dror, O.; Nussinov, R.; Wolfson, H.
- Bioinformatics, Vol. 21, Issue Suppl 2
A modular strategy for generating starting conformations and data structures of polynucleotide helices for potential energy calculations
journal, December 1988
- Schlick, Tamar
- Journal of Computational Chemistry, Vol. 9, Issue 8
The Sarcin/Ricin Loop, a Modular RNA
journal, March 1995
- Szewczak, A. A.; Moore, P. B.
- Journal of Molecular Biology, Vol. 247, Issue 1
Candidates for Novel RNA Topologies
journal, August 2004
- Kim, Namhee; Shiffeldrim, Nahum; Gan, Hin Hark
- Journal of Molecular Biology, Vol. 341, Issue 5
The building blocks and motifs of RNA architecture
journal, June 2006
- Leontis, Neocles B.; Lescoute, Aurelie; Westhof, Eric
- Current Opinion in Structural Biology, Vol. 16, Issue 3
Non–coding RNA genes and the modern RNA world
journal, December 2001
- Eddy, Sean R.
- Nature Reviews Genetics, Vol. 2, Issue 12
Long noncoding RNAs and the genetics of cancer
journal, May 2013
- Cheetham, S. W.; Gruhl, F.; Mattick, J. S.
- British Journal of Cancer, Vol. 108, Issue 12
Revealing the world of RNA interference
journal, September 2004
- Mello, Craig C.; Conte, Darryl
- Nature, Vol. 431, Issue 7006
Long non-coding RNAs: insights into functions
journal, March 2009
- Mercer, Tim R.; Dinger, Marcel E.; Mattick, John S.
- Nature Reviews Genetics, Vol. 10, Issue 3
Non-coding RNAs in human disease
journal, November 2011
- Esteller, Manel
- Nature Reviews Genetics, Vol. 12, Issue 12
Computational approaches to 3D modeling of RNA
journal, June 2010
- Laing, Christian; Schlick, Tamar
- Journal of Physics: Condensed Matter, Vol. 22, Issue 28
RAG: RNA-As-Graphs database--concepts, analysis, and features
journal, February 2004
- Gan, H. H.; Fera, D.; Zorn, J.
- Bioinformatics, Vol. 20, Issue 8
ARTS: alignment of RNA tertiary structures
journal, September 2005
- Dror, O.; Nussinov, R.; Wolfson, H.
- Bioinformatics, Vol. 21, Issue Suppl 2
INFO-RNA--a fast approach to inverse RNA folding
journal, May 2006
- Busch, A.; Backofen, R.
- Bioinformatics, Vol. 22, Issue 15
VARNA: Interactive drawing and editing of the RNA secondary structure
journal, April 2009
- Darty, Kévin; Denise, Alain; Ponty, Yann
- Bioinformatics, Vol. 25, Issue 15
The tmRNA Website: invasion by an intron
journal, January 2002
- Williams, K. P.
- Nucleic Acids Research, Vol. 30, Issue 1
Exploring the repertoire of RNA secondary motifs using graph theory; implications for RNA design
journal, June 2003
- Gan, H. H.
- Nucleic Acids Research, Vol. 31, Issue 11
Modular RNA architecture revealed by computational analysis of existing pseudoknots and ribosomal RNAs
journal, February 2005
- Pasquali, S.
- Nucleic Acids Research, Vol. 33, Issue 4
The ARTS web server for aligning RNA tertiary structures
journal, July 2006
- Dror, O.; Nussinov, R.; Wolfson, H. J.
- Nucleic Acids Research, Vol. 34, Issue Web Server
fRNAdb: a platform for mining/annotating functional RNA candidates from non-coding RNA sequences
journal, January 2007
- Kin, T.; Yamada, K.; Terai, G.
- Nucleic Acids Research, Vol. 35, Issue Database
NONCODE v2.0: decoding the non-coding
journal, December 2007
- He, S.; Liu, C.; Skogerbo, G.
- Nucleic Acids Research, Vol. 36, Issue Database
INFO-RNA—a server for fast inverse RNA folding satisfying sequence constraints
journal, July 2007
- Busch, Anke; Backofen, Rolf
- Nucleic Acids Research, Vol. 35, Issue suppl_2
SARA: a server for function annotation of RNA structures
journal, May 2009
- Capriotti, E.; Marti-Renom, M. A.
- Nucleic Acids Research, Vol. 37, Issue Web Server
WebFR3D--a server for finding, aligning and analyzing recurrent RNA 3D motifs
journal, April 2011
- Petrov, A. I.; Zirbel, C. L.; Leontis, N. B.
- Nucleic Acids Research, Vol. 39, Issue suppl
NASSAM: a server to search for and annotate tertiary interactions and motifs in three-dimensional structures of complex RNA molecules
journal, May 2012
- Hamdani, H. Y.; Appasamy, S. D.; Willett, P.
- Nucleic Acids Research, Vol. 40, Issue W1
RNA Bricks—a database of RNA 3D motifs and their interactions
journal, November 2013
- Chojnowski, Grzegorz; Waleń, Tomasz; Bujnicki, Janusz M.
- Nucleic Acids Research, Vol. 42, Issue D1
Ribo-gnome: The Big World of Small RNAs
journal, September 2005
- Zamore, P. D.
- Science, Vol. 309, Issue 5740
RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures
journal, January 2010
- Popenda, Mariusz; Szachniuk, Marta; Blazewicz, Marek
- BMC Bioinformatics, Vol. 11, Issue 1
Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas
journal, August 2013
- Petrov, A. I.; Zirbel, C. L.; Leontis, N. B.
- RNA, Vol. 19, Issue 10
On the occurrence of the T-loop RNA folding motif in large RNA molecules
journal, June 2003
- Krasilnikov, A. S.
- RNA, Vol. 9, Issue 6
From knotted to nested RNA structures: A variety of computational methods for pseudoknot removal
journal, January 2008
- Smit, S.; Rother, K.; Heringa, J.
- RNA, Vol. 14, Issue 3
Predicting Helical Topologies in RNA Junctions as Tree Graphs
journal, August 2013
- Laing, Christian; Jung, Segun; Kim, Namhee
- PLoS ONE, Vol. 8, Issue 8
miRBase: tools for microRNA genomics.
text, January 2008
- Griffiths-Jones, Sam; Saini, Harpreet Kaur; Van Dongen, Stijn
- Apollo - University of Cambridge Repository
Noncoding RNAs in cancer and cancer stem cells
journal, November 2013
- Huang, Tianzhi; Alvarez, Angel; Hu, Bo
- Chinese Journal of Cancer, Vol. 32, Issue 11
Works referencing / citing this record:
Capturing RNA Folding Free Energy with Coarse-Grained Molecular Dynamics Simulations
journal, April 2017
- Bell, David R.; Cheng, Sara Y.; Salazar, Heber
- Scientific Reports, Vol. 7, Issue 1
A pipeline for computational design of novel RNA-like topologies
journal, June 2018
- Jain, Swati; Laederach, Alain; Ramos, Silvia B. V.
- Nucleic Acids Research, Vol. 46, Issue 14
NAPS update: network analysis of molecular dynamics data and protein–nucleic acid complexes
journal, May 2019
- Chakrabarty, Broto; Naganathan, Varun; Garg, Kanak
- Nucleic Acids Research, Vol. 47, Issue W1
Identification of Structural Motifs Using Networks of Hydrogen-Bonded Base Interactions in RNA Crystallographic Structures
journal, October 2019
- Hamdani, Hazrina Yusof; Firdaus-Raih, Mohd
- Crystals, Vol. 9, Issue 11
Dual Graph Partitioning Highlights a Small Group of Pseudoknot-Containing RNA Submotifs
journal, July 2018
- Jain, Swati; Bayrak, Cigdem; Petingi, Louis
- Genes, Vol. 9, Issue 8
Sizes of Long RNA Molecules Are Determined by the Branching Patterns of Their Secondary Structures
journal, November 2016
- Borodavka, Alexander; Singaram, Surendra W.; Stockley, Peter G.
- Biophysical Journal, Vol. 111, Issue 10
Capturing RNA Folding Free Energy with Coarse-Grained Molecular Dynamics Simulations
journal, April 2017
- Bell, David R.; Cheng, Sara Y.; Salazar, Heber
- Scientific Reports, Vol. 7, Issue 1
Using sequence signatures and kink-turn motifs in knowledge-based statistical potentials for RNA structure prediction
journal, February 2017
- Bayrak, Cigdem Sevim; Kim, Namhee; Schlick, Tamar
- Nucleic Acids Research, Vol. 45, Issue 9
A pipeline for computational design of novel RNA-like topologies
journal, June 2018
- Jain, Swati; Laederach, Alain; Ramos, Silvia B. V.
- Nucleic Acids Research, Vol. 46, Issue 14
Dual Graph Partitioning Highlights a Small Group of Pseudoknot-Containing RNA Submotifs
journal, July 2018
- Jain, Swati; Bayrak, Cigdem; Petingi, Louis
- Genes, Vol. 9, Issue 8