Landscape and variation of RNA secondary structure across the human transcriptome
Open accessAbstract
In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comprehensive RSS map of human coding and non-coding RNAs. We identify unique RSS signatures that demarcate open reading frames and splicing junctions, and define authentic microRNA-binding sites. Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. Over 1,900 transcribed single nucleotide variants (approximately 15% of all transcribed single nucleotide variants) alter local RNA structure. We discover simple sequence and spacing rules that determine the ability of point mutations to impact RSSs. Selective depletion of 'riboSNitches' versus structurally synonymous variants at precise locations suggests selection for specific RNA shapes at thousands of sites, including 3' untranslated regions, binding sites of microRNAs and RNA-binding proteins genome-wide. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation.
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Some studies have shown that protein expression level drops if the 5′-end leader region has more secondary structure.
“Some studies have shown that protein expression level drops if the 5′-end leader region has more secondary structure5,50–53.”
From Algorithm for optimized mRNA design improves stability and immunogenicity (2023) · cites this paper as [51]
The Abstract describes RNA structure near translational start sites, but does not link greater structure in the 5′ leader region to lower protein expression. Searches for 5′-UTR structure, translation efficiency, and protein expression found no passage establishing that relationship. (LLM, conf=0.72)
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Cites
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · see citing works
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068 · see citing works
Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005) · Cell · doi:10.1016/j.cell.2004.12.035 · Cited by 11,855 · see citing works
The International HapMap Project
†The International HapMap Consortium, Genotyping centres: Baylor College of Medicine and ParAllele BioScience, Gibbs, R. A., Belmont, J. W., Hardenbol, P., Willis, T. D., Yu, F., Chinese HapMap Consortium, Yang, H., Ch'ang, L.-Y., et al. (2003) · Nature · doi:10.1038/nature02168 · Cited by 6,057 · see citing works
Self-citationMicroRNA Targeting Specificity in Mammals: Determinants beyond Seed Pairing
Grimson, A., Farh, K. K.-H., Johnston, W. K., Garrett-Engele, P., Lim, L. P., & Bartel, D. P. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.06.017 · Cited by 3,766 · see citing works
Argonaute HITS-CLIP decodes microRNA–mRNA interaction maps
Chi, S. W., Zang, J. B., Mele, A., & Darnell, R. B. (2009) · Nature · doi:10.1038/nature08170 · Cited by 1,791 · see citing works
Analysis and design of RNA sequencing experiments for identifying isoform regulation
Katz, Y., Wang, E. T., Airoldi, E. M., & Burge, C. B. (2010) · Nature Methods · doi:10.1038/nmeth.1528 · Cited by 1,353 · see citing works
iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution
König, J., Zarnack, K., Rot, G., Curk, T., Kayikci, M., Zupan, B., Turner, D. J., Luscombe, N. M., & Ule, J. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1838 · Cited by 1,126 · see citing works
The Evolutionary Landscape of Alternative Splicing in Vertebrate Species
Barbosa-Morais, N. L., Irimia, M., Pan, Q., Xiong, H. Y., Gueroussov, S., Lee, L. J., Slobodeniuc, V., Kutter, C., Watt, S., Çolak, R., et al. (2012) · Science · doi:10.1126/science.1230612 · Cited by 1,063 · see citing works
Barash, Y., Calarco, J. A., Gao, W., Pan, Q., Wang, X., Ofer Shai, A., Blencowe, B. J., & Frey, B. J. (2010) · Nature · doi:10.1038/nature09000 · Cited by 891 · see citing works
Wilkinson, K. A., Merino, E. J., & Weeks, K. M. (2006) · Nature Protocols · doi:10.1038/nprot.2006.249 · Cited by 775 · see citing works
Genome-wide measurement of RNA secondary structure in yeast
Kertesz, M., Wan, Y., Mazor, E., Rinn, J. L., Nutter, R. C., Chang, H. Y., & Segal, E. (2010) · Nature · doi:10.1038/nature09322 · Cited by 765 · see citing works
Self-citationUnderstanding the transcriptome through RNA structure
Wan, Y., Kertesz, M., Spitale, R. C., Segal, E., & Chang, H. Y. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3049 · Cited by 469 · see citing works
Self-citationRNA SHAPE analysis in living cells
Spitale, R. C., Crisalli, P., Flynn, R. A., Torre, E. A., Kool, E. T., & Chang, H. Y. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1131 · Cited by 442 · see citing works
Self-citationThe Viral and Cellular MicroRNA Targetome in Lymphoblastoid Cell Lines
Skalsky, R. L., Corcoran, D., Gottwein, E., Frank, C. L., Kang, D., Hafner, M., Nusbaum, J., Feederle, R., Delecluse, H., Luftig, M., et al. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002484 · Cited by 370 · see citing works
Disease-Associated Mutations That Alter the RNA Structural Ensemble
Halvorsen, M., Martin, J. S., Broadaway, S., & Laederach, A. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001074 · Cited by 325 · see citing works
LIN28 Binds Messenger RNAs at GGAGA Motifs and Regulates Splicing Factor Abundance
Wilbert, M. L., Huelga, S. C., Kapeli, K., Stark, T. J., Liang, T. Y., Chen, S., Yan, B. Y., Nathanson, J. L., Hutt, K. R., Lovci, M., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.08.004 · Cited by 269 · see citing works
DGCR8 HITS-CLIP reveals novel functions for the Microprocessor
Macías, S., Plass, M., Stajuda, A., Michlewski, G., Eyras, E., & Cáceres, J. F. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2344 · Cited by 219 · see citing works
A periodic pattern of mRNA secondary structure created by the genetic code
Shabalina, S. A. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl287 · Cited by 202 · see citing works
doRiNA: a database of RNA interactions in post-transcriptional regulation
Anders, G., Mackowiak, S. D., Jens, M., Maaskola, J., Kuntzagk, A., Rajewsky, N., Landthaler, M., & Dieterich, C. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1007 · Cited by 201 · see citing works
Global Analysis of RNA Secondary Structure in Two Metazoans
Li, F., Zheng, Q., Ryvkin, P., Dragomir, I. C., Desai, Y. B., Aiyer, S., Valladares, O., Yang, J., Bambina, S., Sabin, L. R., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2011.10.002 · Cited by 133 · see citing works
Ouyang, Z., Snyder, M., & Chang, H. Y. (2012) · Genome Research · doi:10.1101/gr.138545.112 · Cited by 115 · see citing works
Self-citationSalari, R., Kimchi‐Sarfaty, C., Gottesman, M. M., & Przytycka, T. M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1009 · Cited by 98 · see citing works
Evaluating our ability to predict the structural disruption of RNA by SNPs
Ritz, J., Martin, J. S., & Laederach, A. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-s4-s6 · Cited by 56 · see citing works
Marín, R. M., Völlmy, F., von Erlach, T., & Vaníček, J. J. L. (2012) · RNA · doi:10.1261/rna.033282.112 · Cited by 18 · see citing works
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Long Noncoding RNAs in Cancer Pathways
Schmitt, A. M., & Chang, H. Y. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.03.010 · Cited by 2,991 · see citing works
Self-citationPost-transcriptional gene regulation by mRNA modifications
Zhao, B. S., Roundtree, I. A., & He, C. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.132 · Cited by 2,418 · see citing works
A census of human RNA-binding proteins
Gerstberger, S., Hafner, M., & Tuschl, T. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3813 · Cited by 2,032 · see citing works
N6-methyladenosine-dependent RNA structural switches regulate RNA–protein interactions
Liu, N., Dai, Q., Zheng, G., He, C., Parisien, M., & Pan, T. (2015) · Nature · doi:10.1038/nature14234 · Cited by 1,988 · see citing works
Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism
Yang, Y., Hsu, P. J., Chen, Y.-S., & Yang, Y. (2018) · Cell Research · doi:10.1038/s41422-018-0040-8 · Cited by 1,683 · see citing works
Context-dependent control of alternative splicing by RNA-binding proteins
Fu, X.-D., & Ares, M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3778 · Cited by 1,044 · see citing works
RNA N 6 -methyladenosine methylation in post-transcriptional gene expression regulationPreprint
Yue, Y., Liu, J., & He, C. (2015) · Genes & Development · doi:10.1101/gad.262766.115 · Cited by 918 · see citing works
N 6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein
Liu, N., Zhou, K. I., Parisien, M., Dai, Q., Diatchenko, L. B., & Pan, T. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx141 · Cited by 786 · see citing works
Structural imprints in vivo decode RNA regulatory mechanisms
Spitale, R. C., Flynn, R. A., Zhang, Q. C., Crisalli, P., Lee, B., Jung, J., Kuchelmeister, H. Y., Batista, P. J., Torre, E. A., Kool, E. T., et al. (2015) · Nature · doi:10.1038/nature14263 · Cited by 745 · see citing works
Self-citationRNA motif discovery by SHAPE and mutational profiling (SHAPE-MaP)
Siegfried, N. A., Busan, S., Rice, G. M., Nelson, J. A. E., & Weeks, K. M. (2014) · Nature Methods · doi:10.1038/nmeth.3029 · Cited by 662 · see citing works
Targeting RNA structures with small molecules
Childs‐Disney, J. L., Yang, X., Gibaut, Q. M. R., Tong, Y., Batey, R., & Disney, M. D. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00521-4 · Cited by 599 · see citing works
mRNA structure regulates protein expression through changes in functional half-life
Mauger, D. M., Cabral, B. J., Presnyak, V., Su, S. V., Reid, D. W., Goodman, B., Link, K., Khatwani, N., Reynders, J., Moore, M. J., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908052116 · Cited by 555 · see citing works
NONCODEV5: a comprehensive annotation database for long non-coding RNAs
Fang, S., Zhang, L., Guo, J., Niu, Y., Wu, Y., Li, H., Zhao, L., Li, X., Teng, X., Sun, X., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1107 · Cited by 548 · see citing works
Algorithm for optimized mRNA design improves stability and immunogenicity
Zhang, H., Zhang, L., Lin, A., Xu, C., Li, Z., Liu, K., Liu, B., Ma, X., Zhao, F., Jiang, H., et al. (2023) · Nature · doi:10.1038/s41586-023-06127-z · Cited by 498 · see citing works
Insights into RNA structure and function from genome-wide studies
Mortimer, S., Kidwell, M. A., & Doudna, J. A. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3681 · Cited by 465 · see citing works
Impact of regulatory variation from RNA to protein
Battle, A., Khan, Z., Wang, S. H., Mitrano, A., Ford, M. J., Pritchard, J. K., & Gilad, Y. (2015) · Science · doi:10.1126/science.1260793 · Cited by 471 · see citing works
DMS-MaPseq for genome-wide or targeted RNA structure probing in vivo
Zubradt, M. M., Gupta, P., Persad, S., Lambowitz, A. M., Weissman, J. S., & Rouskin, S. (2016) · Nature Methods · doi:10.1038/nmeth.4057 · Cited by 460 · see citing works
Briggs, J., Wolvetang, E. J., Mattick, J. S., Rinn, J. L., & Barry, G. (2015) · Neuron · doi:10.1016/j.neuron.2015.09.045 · Cited by 443 · see citing works
Revealing lncRNA Structures and Interactions by Sequencing-Based Approaches
Qian, X., Zhao, J., Yeung, P. Y., Zhang, Q. C., & Kwok, C. K. (2018) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2018.09.012 · Cited by 436 · see citing works
Self-citationStructure and Thermodynamics of N 6 -Methyladenosine in RNA: A Spring-Loaded Base Modification
Roost, C., Lynch, S. R., Batista, P. J., Qu, K., Chang, H. Y., & Kool, E. T. (2015) · Journal of the American Chemical Society · doi:10.1021/ja513080v · Cited by 416 · see citing works
Self-citationFrom Discovery to Function: The Expanding Roles of Long NonCoding RNAs in Physiology and Disease
Sun, M., & Kraus, W. L. (2014) · Endocrine Reviews · doi:10.1210/er.2014-1034 · Cited by 392 · see citing works
Global Mapping of Human RNA-RNA Interactions
Sharma, E., Sterne‐Weiler, T., O’Hanlon, D., & Blencowe, B. J. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.04.030 · Cited by 385 · see citing works
Aw, J. G. A., Shen, Y., Wilm, A., Sun, M., Lim, X. N., Boon, K.-L., Tapşın, S., Chan, Y.-S., Tan, C.-P., Sim, A. Y. L., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.04.028 · Cited by 342 · see citing works
Self-citationAlternative mRNA transcription, processing, and translation: insights from RNA sequencing
de Klerk, E., & ‘t Hoen, P. A. C. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.01.001 · Cited by 350 · see citing works
RNA modifications and structures cooperate to guide RNA–protein interactions
Lewis, C. J. T., Pan, T., & Kalsotra, A. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.163 · Cited by 309 · see citing works
Dynamic methylome of internal mRNA N7-methylguanosine and its regulatory role in translation
Malbec, L., Zhang, T., Chen, Y., Zhang, Y., Sun, B., Shi, B., Zhao, Y., Yang, Y., & Yang, Y. (2019) · Cell Research · doi:10.1038/s41422-019-0230-z · Cited by 304 · see citing works
Specificity and nonspecificity in RNA–protein interactions
Jankowsky, E., & Harris, M. E. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4032 · Cited by 277 · see citing works
hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1
Sugimoto, Y., Vigilante, A., Darbo, É., Zirra, A., Militti, C., D’Ambrogio, A., Luscombe, N. M., & Ule, J. (2015) · Nature · doi:10.1038/nature14280 · Cited by 270 · see citing works
Non-coding RNA: a new frontier in regulatory biology
Fu, X. (2014) · National Science Review · doi:10.1093/nsr/nwu008 · Cited by 257 · see citing works
Pervasive Regulatory Functions of mRNA Structure Revealed by High-Resolution SHAPE Probing
Mustoe, A. M., Busan, S., Rice, G. M., Hajdin, C. E., Peterson, B. K., Ruda, V. M., Kubica, N., Nutiu, R., Baryza, J. L., & Weeks, K. M. (2018) · Cell · doi:10.1016/j.cell.2018.02.034 · Cited by 259 · see citing works
Coupling of RNA Polymerase II Transcription Elongation with Pre-mRNA Splicing
Saldi, T. K., Cortázar, M. A., Sheridan, R. M., & Bentley, D. L. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.04.017 · Cited by 246 · see citing works
RNA structure maps across mammalian cellular compartments
Sun, L., Fazal, F. M., Li, P., Broughton, J. P., Lee, B., Tang, L., Huang, W., Kool, E. T., Chang, H. Y., & Zhang, Q. C. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0200-7 · Cited by 239 · see citing works
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Tomezsko, P. J., Corbin, V., Gupta, P., Swaminathan, H., Glasgow, M., Persad, S., Edwards, M. D., McIntosh, L., Papenfuss, A. T., Emery, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2253-5 · Cited by 228 · see citing works
Genome-Wide Analysis of RNA Secondary Structure
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Long non-coding RNAs as regulators of the endocrine system
Knoll, M., Lodish, H. F., & Sun, L. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.229 · Cited by 220 · see citing works
Thoughts on how to think (and talk) about RNA structure
Vicens, Q., & Kieft, J. S. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2112677119 · Cited by 209 · see citing works
Kashi, K., Henderson, L., Bonetti, A., & Carninci, P. (2015) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2015.10.010 · Cited by 204 · see citing works
The roles of RNA processing in translating genotype to phenotype
Manning, K. S., & Cooper, T. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.139 · Cited by 206 · see citing works
Genetic variants in mRNA untranslated regions
Steri, M., Idda, M. L., Whalen, M. B., & Orrù, V. (2018) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1474 · Cited by 200 · see citing works
RNA structure drives interaction with proteins
de Groot, N. S., Armaos, A., Montes, R. G., Alriquet, M., Calloni, G., Vabulas, R. M., & Tartaglia, G. G. (2019) · Nature Communications · doi:10.1038/s41467-019-10923-5 · Cited by 193 · see citing works
Platforms for Investigating LncRNA Functions
Richard, J. L. C., & Eichhorn, P. J. A. (2018) · SLAS TECHNOLOGY · doi:10.1177/2472630318780639 · Cited by 187 · see citing works
High-throughput determination of RNA structures
Strobel, E. J., Yu, A. M., & Lucks, J. B. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0034-x · Cited by 188 · see citing works
Zhang, Z. S., Luo, K., Zou, Z., Qiu, M., Tian, J., Sieh, L., Shi, H., Zou, Y., Wang, G. T., Morrison, J., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0644-z · Cited by 187 · see citing works
Campo, C. D., Bartholomäus, A., Fedyunin, I., & Ignatova, Z. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005613 · Cited by 178 · see citing works
Wang, Y., Kumari, M., Chen, G., Hong, M.-H., Yuan, J. P., Tsai, J.-L., & Wu, H. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00977-5 · Cited by 183 · see citing works
Linking RNA biology to lncRNAsPreprint
Goff, L. A., & Rinn, J. L. (2015) · Genome Research · doi:10.1101/gr.191122.115 · Cited by 175 · see citing works
Noncoding RNA and its associated proteins as regulatory elements of the immune system
Turner, M., Galloway, A., & Vigorito, E. (2014) · Nature Immunology · doi:10.1038/ni.2887 · Cited by 172 · see citing works
Li, L., Huang, K.-L., Gao, Y., Cui, Y., Wang, G. T., Elrod, N. D., Li, Y., Chen, Y. E., Ji, P., Peng, F., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00864-5 · Cited by 172 · see citing works
Operon mRNAs are organized into ORF-centric structures that predict translation efficiency
Burkhardt, D. H., Rouskin, S., Zhang, Y., Li, G., Weissman, J. S., & Gross, C. A. (2017) · eLife · doi:10.7554/elife.22037 · Cited by 163 · see citing works
3D RNA and Functional Interactions from Evolutionary Couplings
Weinreb, C., Riesselman, A. J., Ingraham, J. B., Gross, T., Sander, C., & Marks, D. S. (2016) · Cell · doi:10.1016/j.cell.2016.03.030 · Cited by 159 · see citing works
Direct detection of RNA modifications and structure using single-molecule nanopore sequencing
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Gennarino, V. A., Singh, R. K., White, J. J., Maio, A. D., Han, K., Kim, J., Jafar‐Nejad, P., di Ronza, A., Kang, H., Sayegh, L. S., et al. (2015) · Cell · doi:10.1016/j.cell.2015.02.012 · Cited by 149 · see citing works
Advances and opportunities in RNA structure experimental determination and computational modeling
Zhang, J., Fei, Y., Sun, L., & Zhang, Q. C. (2022) · Nature Methods · doi:10.1038/s41592-022-01623-y · Cited by 148 · see citing works
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Self-citationTailor made: the art of therapeutic mRNA design
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The RNA structurome: transcriptome-wide structure probing with next-generation sequencing
Kwok, C. K., Tang, Y., Assmann, S. M., & Bevilacqua, P. C. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.02.005 · Cited by 144 · see citing works
Loughrey, D., Watters, K. E., Settle, A. H., & Lucks, J. B. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku909 · Cited by 141 · see citing works
Technologies to probe functions and mechanisms of long noncoding RNAs
Chu, C., Spitale, R. C., & Chang, H. Y. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2921 · Cited by 136 · see citing works
Self-citationBridging the gap betweenin vitroandin vivoRNA folding
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Role of mRNA structure in the control of protein folding
Faure, G., Ogurtsov, A. Y., Shabalina, S. A., & Koonin, E. V. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw671 · Cited by 134 · see citing works
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Advances in long noncoding RNAs: identification, structure prediction and function annotation
Guo, X., Gao, L., Wang, Y., Chiu, D., Wang, T., & Deng, Y. C. (2015) · Briefings in Functional Genomics · doi:10.1093/bfgp/elv022 · Cited by 131 · see citing works
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Self-citationSolomon, O., Segni, A. D., Cesarkas, K., Porath, H. T., Marcu‐Malina, V., Mizrahi, O., Stern‐Ginossar, N., Kol, N., Barhom, S. F., Glick‐Saar, E., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01458-8 · Cited by 128 · see citing works
Incarnato, D., Neri, F., Anselmi, F., & Oliviero, S. (2014) · Genome biology · doi:10.1186/s13059-014-0491-2 · Cited by 124 · see citing works
Targeting RNA in mammalian systems with small molecules
Donlic, A., & Hargrove, A. E. (2018) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1477 · Cited by 122 · see citing works
Analyses of mRNA structure dynamics identify embryonic gene regulatory programs
Beaudoin, J.-D., Novoa, E. M., Vejnar, C. E., Yartseva, V., Takacs, C. M., Kellis, M., & Giráldez, A. J. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0091-z · Cited by 124 · see citing works
DNA methylation directs microRNA biogenesis in mammalian cells
Glaich, O., Parikh, S., Bell, R. E., Mekahel, K., Donyo, M., Leader, Y., Shayevitch, R., Sheinboim, D., Yannai, S., Hollander, D., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13527-1 · Cited by 124 · see citing works
Rocca, G. L., Olejniczak, S. H., González, A. J., Briskin, D., Vidigal, J. A., Spraggon, L., Dematteo, R. G., Radler, M. R., Lindsten, T., Ventura, A., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1424217112 · Cited by 117 · see citing works
Long non-coding RNAs in human early embryonic development and their potential in ART
Bouckenheimer, J., Assou, S., Riquier, S., Hou, C., Philippe, N., Sansac, C., Lavabre‐Bertrand, T., Commes, T., Lemaı̂tre, J.-M., Boureux, A., et al. (2016) · Human Reproduction Update · doi:10.1093/humupd/dmw035 · Cited by 119 · see citing works
Identification of RNA structures and their roles in RNA functions
Cao, X., Zhang, Y., Ding, Y., & Wan, Y. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00748-6 · Cited by 115 · see citing works
Self-citationThe Maternal-to-Zygotic Transition During Vertebrate Development
Yartseva, V., & Giráldez, A. J. (2015) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2015.07.020 · Cited by 110 · see citing works
Determination of isoform-specific RNA structure with nanopore long reads
Aw, J. G. A., Lim, S. W., Wang, J., Lambert, F. R. P., Tan, W. T., Shen, Y., Zhang, Y., Kaewsapsak, P., Li, C., Ng, S. B. H., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0712-z · Cited by 112 · see citing works
Self-citationA Variety of Dicer Substrates in Human and C. elegans
Rybak‐Wolf, A., Jens, M., Murakawa, Y., Herzog, M., Landthaler, M., & Rajewsky, N. (2014) · Cell · doi:10.1016/j.cell.2014.10.040 · Cited by 111 · see citing works
Genome-wide RNA structurome reprogramming by acute heat shock globally regulates mRNA abundance
Su, Z. Z., Tang, Y., Ritchey, L. E., Tack, D. C., Zhu, M., Bevilacqua, P. C., & Assmann, S. M. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1807988115 · Cited by 111 · see citing works
High-throughput determination of RNA structure by proximity ligation
Ramani, V., Qiu, R., & Shendure, J. (2015) · Nature Biotechnology · doi:10.1038/nbt.3289 · Cited by 108 · see citing works
RNA folding with hard and soft constraints
Lorenz, R., Hofacker, I. L., & Stadler, P. F. (2016) · Algorithms for Molecular Biology · doi:10.1186/s13015-016-0070-z · Cited by 106 · see citing works
Strategies to Annotate and Characterize Long Noncoding RNAs: Advantages and Pitfalls
Cao, H., Wahlestedt, C., & Kapranov, P. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.06.002 · Cited by 105 · see citing works
The identification and functional annotation of RNA structures conserved in vertebratesPreprint
Seemann, S. E., Mirza, A. H., Hansen, C., Bang‐Berthelsen, C. H., Garde, C., Christensen‐Dalsgaard, M., Torarinsson, E., Yao, Z., Workman, C. T., Pociot, F., et al. (2017) · Genome Research · doi:10.1101/gr.208652.116 · Cited by 105 · see citing works
The Conservation and Function of RNA Secondary Structure in Plants
Vandivier, L. E., Anderson, S. J., Foley, S. W., & Gregory, B. D. (2016) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-043015-111754 · Cited by 101 · see citing works
Understanding the Functions of Long Non-Coding RNAs through Their Higher-Order Structures
Li, R., Zhu, H., & Luo, Y. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17050702 · Cited by 101 · see citing works
Realizing the significance of noncoding functionality in clinical genomics
Gloss, B., & Dinger, M. E. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0087-0 · Cited by 98 · see citing works
A general fragment-based approach to identify and optimize bioactive ligands targeting RNA
Suresh, B. M., Li, W., Zhang, P., Wang, K. W., Yildirim, I., Parker, C. G., & Disney, M. D. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2012217117 · Cited by 100 · see citing works
Genome-wide profiling of in vivo RNA structure at single-nucleotide resolution using structure-seq
Ding, Y., Kwok, C. K., Tang, Y., Bevilacqua, P. C., & Assmann, S. M. (2015) · Nature Protocols · doi:10.1038/nprot.2015.064 · Cited by 98 · see citing works
Warth, S. C., Hoefig, K. P., Hiekel, A., Schallenberg, S., Jovanovic, K., Klein, L., Kretschmer, K., Ansel, K. M., & Heissmeyer, V. (2015) · The EMBO Journal · doi:10.15252/embj.201489589 · Cited by 99 · see citing works
The landscape of eukaryotic mRNPs
Khong, A., & Parker, R. (2019) · RNA · doi:10.1261/rna.073601.119 · Cited by 93 · see citing works
Hazen, J. L., Faust, G. G., Rodriguez, A. R., Ferguson, W. C., Shumilina, S., Clark, R. A., Boland, M. J., Martin, G., Chubukov, P., Tsunemoto, R. K., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.02.004 · Cited by 92 · see citing works
Long non-coding RNA and tumor hypoxia: new players ushered toward an old arena
Shih, J.-W., & Kung, H. (2017) · Journal of Biomedical Sciences · doi:10.1186/s12929-017-0358-4 · Cited by 85 · see citing works
Long non-coding RNAs in ovarian cancer
Zhan, L., Li, J., & Wei, B. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0793-4 · Cited by 88 · see citing works
Balaško, M. K., Mikac, K. M., Bažok, R., & Lemić, D. (2020) · Insects · doi:10.3390/insects11090581 · Cited by 90 · see citing works
The regulatory impact of RNA-binding proteins on microRNA targeting
Kim, S., Kim, S., Chang, H. R., Kim, D., Park, J., Son, N., Park, J., Yoon, M., Chae, G., Kim, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25078-5 · Cited by 87 · see citing works
Self-citationWu, Y., Shi, B., Ding, X., Liu, T., Hu, X. S., Yip, K. Y.-L., Yang, Z. R., Mathews, D. H., & Lu, Z. J. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv706 · Cited by 86 · see citing works
Cid-Samper, F., Gelabert‐Baldrich, M., Lang, B., Lorenzo-Gotor, N., Ponti, R. D., Severijnen, L.-A. W. F. M., Bolognesi, B., Gelpí, E., Hukema, R. K., Botta‐Orfila, T., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.076 · Cited by 86 · see citing works
Functions and properties of nuclear lncRNAs—from systematically mapping the interactomes of lncRNAs
Guh, C.-Y., Hsieh, Y.-H., & Chu, H.-P. C. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00640-3 · Cited by 86 · see citing works
Pervasive downstream RNA hairpins dynamically dictate start-codon selection
Xiang, Y.-Z., Huang, W.-Z., Tan, L., Chen, T.-Y., He, Y., Irving, P. S., Weeks, K., Zhang, Q., & Dong, X.-N. (2023) · Nature · doi:10.1038/s41586-023-06500-y · Cited by 74 · see citing works
Self-citationLi, M. J., Yan, B., Sham, P. C., & Wang, J. (2014) · Briefings in Bioinformatics · doi:10.1093/bib/bbu018 · Cited by 83 · see citing works
Microprocessor Activity Controls Differential miRNA Biogenesis In Vivo
Conrad, T., Marsico, A., Gehre, M., & Ørom, U. A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.09.007 · Cited by 85 · see citing works
High-throughput characterization of protein-RNA interactions
Cook, K. B., Hughes, T., & Morris, Q. (2014) · Briefings in Functional Genomics · doi:10.1093/bfgp/elu047 · Cited by 82 · see citing works
- Authors
- Wan, Y., Qu, K., Zhang, Q. C., Flynn, R. A., Manor, O., Ouyang, Z., Zhang, J., Spitale, R. C., Snyder, M. P., Segal, E., & Chang, H. Y.
- Affiliations
- Howard Hughes Medical Institute (US)
- Weizmann Institute of Science (IL)
- Stanford Medicine (US)
- Corresponding author
- Wan, Yue
- Chang, Howard Y.
- ORCID
- Venue
- Nature
- Published
- 2014-01-29
- Volume
- 505
- Issue
- 7485
- Pages
- 706-709
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3973747
- OpenAlex
- W2071717527
- Cited by
- 555
- References
- 26
- Citations by year
- 2026: 29 · 2025: 24 · 2024: 26 · 2023: 30 · 2022: 40 · 2021: 50 · 2020: 52 · 2019: 37 · 2018: 61 · 2017: 40 · 2016: 56 · 2015: 71 · 2014: 39
- FWCI
- 28.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Human Genome Research Institute (R01HG004361)
- National Cancer Institute (T32CA009302, P30CA034196)
- 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 › RNA regulation and disease
- Keywords
- RNA secondary structure, human transcriptome, single nucleotide variants, RNA structure prediction, gene expression regulation, single-stranded RNA, Arabidopsis thaliana, yeast, non-coding RNA, splice sites, polyadenylation
- MeSH terms
- Base Sequence, Binding Sites, Child, Female, Gene Expression Regulation, Humans, Male, Nucleic Acid Conformation, RNA, Genome, Human, Open Reading Frames, RNA-Binding Proteins, Point Mutation, 3' Untranslated Regions, RNA Splice Sites, MicroRNAs, Transcriptome
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