Discovering RNA-Protein Interactome by Using Chemical Context Profiling of the RNA-Protein Interface
Open accessAbstract
RNA-protein (RNP) interactions generally are required for RNA function. At least 5% of human genes code for RNA-binding proteins. Whereas many approaches can identify the RNA partners for a specific protein, finding the protein partners for a specific RNA is difficult. We present a machine-learning method that scores a protein's binding potential for an RNA structure by utilizing the chemical context profiles of the interface from known RNP structures. Our approach is applicable even when only a single RNP structure is available. We examined 801 mammalian proteins and find that 37 (4.6%) potentially bind transfer RNA (tRNA). Most are enzymes involved in cellular processes unrelated to translation and were not known to interact with RNA. We experimentally tested six positive and three negative predictions for tRNA binding in vivo, and all nine predictions were correct. Our computational approach provides a powerful complement to experiments in discovering new RNPs.
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A human tRNA microarray has been developed for tRNA quantification and has been applied in tRNA profiling in HIV-1, specific human tissues and tumor cells, and in identifying the complete interactome of tRNA-binding proteins.
“A human tRNA microarray has been developed for tRNA quantification and has been applied in tRNA profiling in HIV-1 (51), as well as of specific human tissues and tumor cells, and in identifying the complete interactome of tRNA-binding proteins (136 -138).”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [138]
The Experimental Procedures (UV CLIP-Chip; page not provided) say previously developed tRNA microarrays determine tRNA abundance, and this study used them to identify tRNAs bound to selected proteins. But the Results (Cognate versus Generic tRNA; page not provided) explicitly say the method will not identify all tRNA-binding proteins, so it does not support a complete interactome. This paper also does not establish the stated profiling of human tissues and tumor cells. (LLM, conf=0.91)
Experimental — accuracy not yet measured
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Cites
HITS-CLIP yields genome-wide insights into brain alternative RNA processing
Licatalosi, D. D., Mele, A., Fak, J. J., Ule, J., Kayikci, M., Chi, S. W., Clark, T. A., Schweitzer, A. C., Blume, J. E., Wang, X., et al. (2008) · Nature · doi:10.1038/nature07488 · Cited by 1,352 · cited 2× · see citing works
“1710 Cell Reports 3, 1703–1713, May 30, 2013 ª2013 The Authors The six tRNA-binding proteins have broad binding selectivity for tRNA, similar to many mRNA-binding proteins that recognize broad sequence/structural motifs in manymRNAs (Ascano et al., 2012; Licatalosi et al., 2008).”
BackgroundSelf-citationCLIP Identifies Nova-Regulated RNA Networks in the Brain
Ule, J., Jensen, K. B., Ruggiu, M., Mele, A., Ule, A., & Darnell, R. B. (2003) · Science · doi:10.1126/science.1090095 · Cited by 1,120 · see citing works
Integrative Modeling Defines the Nova Splicing-Regulatory Network and Its Combinatorial Controls
Zhang, C., Frias, M. A., Mele, A., Ruggiu, M., Eom, T., Marney, C. B., Wang, H., Licatalosi, D. D., Fak, J. J., & Darnell, R. B. (2010) · Science · doi:10.1126/science.1191150 · Cited by 294 · see citing works
Systematic discovery of structural elements governing stability of mammalian messenger RNAs
Goodarzi, H., Najafabadi, H. S., Oikonomou, P., Greco, T. M., Fish, L., Salavati, R., Cristea, I. M., & Tavazoie, S. (2012) · Nature · doi:10.1038/nature11013 · Cited by 187 · see citing works
Flagged first, then by citations
Research works printed but not linked: 53
- Agostini F Cirillo D Bolognesi B Tartaglia GG X-inactivation: quantitative predictions of protein interactions in the Xist network Nucleic Acids Res 2013 41 e31 23093590 PMC3592426
- Ahmad S Sarai A Analysis of electric moments of RNA-binding proteins: implications for mechanism and prediction BMC Struct. Biol 2011 11 8 21284850 PMC3048485
- Ascano M Hafner M Cekan P Gerstberger S Tuschl T Identification of RNA-protein interaction networks using PAR-CLIP Wiley Interdiscip. Rev. RNA 2012 3 159 177 22213601 PMC3711140
- Attwood TK The PRINTS database: a resource for identification of protein families Brief. Bioinform 2002 3 252 263 12230034
- Bahadur RP Zacharias M Janin J Dissecting protein-RNA recognition sites Nucleic Acids Res 2008 36 2705 2716 18353859 PMC2377425
- Baltz AG Munschauer M Schwanhäusser B Vasile A Murakawa Y Schueler M Youngs N Penfold-Brown D Drew K Milek M The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts Mol. Cell 2012 46 674 690 22681889
- Bellucci M Agostini F Masin M Tartaglia GG Predicting protein associations with long noncoding RNAs Nat. Methods 2011 8 444 445 21623348
- Berman H Henrick K Nakamura H Markley JL The worldwide Protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data Nucleic Acids Res 2007 35 D301 D303 (Databaseissue) 17142228 PMC1669775
- Castello A Fischer B Eichelbaum K Horos R Beckmann BM Strein C Davey NE Humphreys DT Preiss T Steinmetz LM Insights into RNA biology from an atlas of mammalian mRNA-binding proteins Cell 2012 149 1393 1406 22658674
- Chan PP Lowe TM GtRNAdb: a database of transfer RNA genes detected in genomic sequence Nucleic Acids Res 2009 37 D93 D97 (Databaseissue) 18984615 PMC2686519
- Chen YC Lim C Predicting RNA-binding sites from the protein structure based on electrostatics, evolution and geometry Nucleic Acids Res 2008 36 e29 18276647 PMC2275128
- Chruszcz M Domagalski M Osinski T Wlodawer A Minor W Unmet challenges of structural genomics Curr. Opin. Struct. Biol 2010 20 587 597 20810277 PMC3017768
- Cruz JA Blanchet MF Boniecki M Bujnicki JM Chen SJ Cao S Das R Ding F Dokholyan NV Flores SC RNA-Puzzles: a CASP-like evaluation of RNA three-dimensional structure prediction RNA 2012 18 610 625 22361291 PMC3312550
- Dittmar KA Goodenbour JM Pan T Tissue-specific differences in human transfer RNA expression PLoS Genet 2006 2 e221 17194224 PMC1713254
- Draper DE Themes in RNA-protein recognition J. Mol. Biol 1999 293 255 270 10550207
- Ellis JJ Jones S Evaluating conformational changes in protein structures binding RNA Proteins 2008 70 1518 1526 17910059
- England TE Bruce AG Uhlenbeck OC Specific labeling of 3′ termini of RNA with T4 RNA ligase Methods Enzymol 1980 65 65 74 6154874
- Fulle S Gohlke H Molecular recognition of RNA: challenges for modelling interactions and plasticity J. Mol. Recognit 2010 23 220 231 19941322
- Gabb HA Jackson RM Sternberg MJ Modelling protein docking using shape complementarity, electrostatics and biochemical information J. Mol. Biol 1997 272 106 120 9299341
- Hafner M Landthaler M Burger L Khorshid M Hausser J Berninger P Rothballer A Ascano M Jr Jungkamp AC Munschauer M Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP Cell 2010 141 129 141 20371350 PMC2861495
- Hinnebusch AG Natarajan K Gcn4p, a master regulator of gene expression, is controlled at multiple levels by diverse signals of starvation and stress Eukaryot. Cell 2002 1 22 32 12455968 PMC118051
- Hunter S Apweiler R Attwood TK Bairoch A Bateman A Binns D Bork P Das U Daugherty L Duquenne L InterPro: the integrative protein signature database Nucleic Acids Res 2009 37 D211 D215 (Databaseissue) 18940856 PMC2686546
- Kim OT Yura K Go N Amino acid residue doublet propensity in the protein-RNA interface and its application to RNA interface prediction Nucleic Acids Res 2006 34 6450 6460 17130160 PMC1761430
- Kondo J Westhof E Classification of pseudo pairs between nucleotide bases and amino acids by analysis of nucleotide-protein complexes Nucleic Acids Res 2011 39 8628 8637 21737431 PMC3201857
- Li CH Cao LB Su JG Yang YX Wang CX A new residue-nucleotide propensity potential with structural information considered for discriminating protein-RNA docking decoys Proteins 2012a 80 14 24 21953889
- Li M Kao E Gao X Sandig H Limmer K Pavon-Eternod M Jones TE Landry S Pan T Weitzman MD David M Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11 Nature 2012b 491 125 128 23000900 PMC3705913
- Lunde BM Moore C Varani G RNA-binding proteins: modular design for efficient function Nat. Rev. Mol. Cell Biol 2007 8 479 490 17473849 PMC5507177
- Motorin Y Helm M tRNA stabilization by modified nucleotides Biochemistry 2010 49 4934 4944 20459084
- Moult J Fidelis K Kryshtafovych A Tramontano A Critical assessment of methods of protein structure prediction (CASP)— round IX Proteins 2011 79 Suppl 10 1 5 21997831 PMC4180088
- Netzer N Goodenbour JM David A Dittmar KA Jones RB Schneider JR Boone D Eves EM Rosner MR Gibbs JS Innate immune and chemically triggered oxidative stress modifies translational fidelity Nature 2009 462 522 526 19940929 PMC2785853
- Novoa EM Pavon-Eternod M Pan T Ribas de Pouplana L A role for tRNA modifications in genome structure and codon usage Cell 2012 149 202 213 22464330
- Parisien M Freed KF Sosnick TR On docking, scoring and assessing protein-DNA complexes in a rigid-body framework PLoS One 2012 7 e32647 22393431 PMC3290582
- Pavon-Eternod M Gomes S Geslain R Dai Q Rosner MR Pan T tRNA over-expression in breast cancer and functional consequences Nucleic Acids Res 2009 37 7268 7280 19783824 PMC2790902
- Pérez-Cano L Fernández-Recio J Optimal protein-RNA area, OPRA: a propensity-based method to identify RNA-binding sites on proteins Proteins 2010 78 25 35 19714772
- Polozov RV Montrel M Ivanov VV Melnikov Y Sivozhelezov VS Transfer RNAs: electrostatic patterns and an early stage of recognition by synthetases and elongation factor EF-Tu Biochemistry 2006 45 4481 4490 16584184
- Pons C Solernou A Perez-Cano L Grosdidier S Fernandez-Recio J Optimization of pyDock for the new CAPRI challenges: docking of homology-based models, domain-domain assembly and protein-RNA binding Proteins 2010 78 3182 3188 20602351
- Puton T Kozlowski L Tuszynska I Rother K Bujnicki JM Computational methods for prediction of protein-RNA interactions J. Struct. Biol 2012 179 261 268 22019768
- Romero E Sopena JM Performing feature selection with multilayer perceptrons IEEE Trans. Neural Netw 2008 19 431 441 18334363
- Scheibe M Butter F Hafner M Tuschl T Mann M Quantitative mass spectrometry and PAR-CLIP to identify RNA-protein interactions Nucleic Acids Res 2012 40 9897 9902 22885304 PMC3479200
- Serganov A Patel DJ Towards deciphering the principles underlying an mRNA recognition code Curr. Opin. Struct. Biol 2008 18 120 129 18255277 PMC3744885
- Setny P Zacharias M A coarse-grained force field for Protein-RNA docking Nucleic Acids Res 2011 39 9118 9129 21846771 PMC3241652
- Shajani Z Sykes MT Williamson JR Assembly of bacterial ribosomes Annu. Rev. Biochem 2011 80 501 526 21529161
- Shazman S Mandel-Gutfreund Y Classifying RNA-binding proteins based on electrostatic properties PLoS Comput. Biol 2008 4 e1000146 18716674 PMC2518515
- Shulman-Peleg A Shatsky M Nussinov R Wolfson HJ Prediction of interacting single-stranded RNA bases by protein-binding patterns J. Mol. Biol 2008 379 299 316 18452949 PMC2429989
- Sternberg MJ Gabb HA Jackson RM Moont G Protein-protein docking. Generation and filtering of complexes Methods Mol. Biol 2000 143 399 415 11084916
- Tuszynska I Bujnicki JM DARS-RNP and QUASI-RNP: new statistical potentials for protein-RNA docking BMC Bioinformatics 2011 12 348 21851628 PMC3179970
- Tworowski D Safro M The long-range electrostatic interactions control tRNA-aminoacyl-tRNA synthetase complex formation Protein Sci 2003 12 1247 1251 12761395 PMC2323892
- Tworowski D Feldman AV Safro MG Electrostatic potential of aminoacyl-tRNA synthetase navigates tRNA on its pathway to the binding site J. Mol. Biol 2005 350 866 882 15964014
- Uhlen M Oksvold P Fagerberg L Lundberg E Jonasson K Forsberg M Zwahlen M Kampf C Wester K Hober S Towards a knowledge-based Human Protein Atlas Nat. Biotechnol 2010 28 1248 1250 21139605
- Ule J Jensen K Mele A Darnell RB CLIP: a method for identifying protein-RNA interaction sites in living cells Methods 2005 37 376 386 16314267
- Zhang C Darnell RB Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data Nat. Biotechnol 2011 29 607 614 21633356 PMC3400429
- Zhao H Yang Y Zhou Y Structure-based prediction of RNA-binding domains and RNA-binding sites and application to structural genomics targets Nucleic Acids Res 2011 39 3017 3025 21183467 PMC3082898
- Zheng S Robertson TA Varani G A knowledge-based potential function predicts the specificity and relative binding energy of RNA-binding proteins FEBS J 2007 274 6378 6391 18005254
Cited by
Sorted by citations
Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication
Jin, D., & Musier-Forsyth, K. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.rev118.002957 · Cited by 67 · see citing works
- Authors
- Parisien, M., Wang, X., Perdrizet, G., Lamphear, C., Fierke, C. A., Maheshwari, K. C., Wilde, M. J., Sosnick, T. R., & Pan, T.
- Affiliations
- University of Chicago (US)
- University of Michigan (US)
- Corresponding author
- Sosnick, Tobin R.
- Pan, Tao
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 3
- Issue
- 5
- Pages
- 1703-1713
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC3769137
- OpenAlex
- W2165955313
- Cited by
- 28
- References
- 4
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- University of Chicago
- National Institutes of Health
- Natural Sciences and Engineering Research Council of Canada
- National Institute of General Medical Sciences (R56GM057880, R01GM057880, GM57880)
- National Center for Research Resources (S10RR029030)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- RNA-protein interactions, RNA-binding proteins, tRNA binding, protein binding prediction, machine learning, mammalian proteins
- MeSH terms
- Humans, Nucleic Acid Conformation, Protein Binding, RNA, Transfer, RNA-Binding Proteins, Computational Biology, Databases, Protein, HEK293 Cells, Nucleotide Motifs, Molecular Docking Simulation
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