Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression
Open accessAbstract
We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc)RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes, including cell-cycle regulation, immune surveillance, and embryonic stem cell pluripotency. However, the mechanism by which these lincRNAs function is unknown. Here, we expand the catalog of human lincRNAs to ≈3,300 by analyzing chromatin-state maps of various human cell types. Inspired by the observation that the well-characterized lincRNA HOTAIR binds the polycomb repressive complex (PRC)2, we tested whether many lincRNAs are physically associated with PRC2. Remarkably, we observe that ≈20% of lincRNAs expressed in various cell types are bound by PRC2, and that additional lincRNAs are bound by other chromatin-modifying complexes. Also, we show that siRNA-mediated depletion of certain lincRNAs associated with PRC2 leads to changes in gene expression, and that the up-regulated genes are enriched for those normally silenced by PRC2. We propose a model in which some lincRNAs guide chromatin-modifying complexes to specific genomic loci to regulate gene expression.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several noncoding RNAs, including microRNAs and long noncoding RNAs such as TUG1, miR-34, lincRNA-p21, PANDA and PINT, were reported to mediate p53-dependent gene regulation.
“Several noncoding RNAs were reported to mediate p53-dependent gene regulation—these include microRNAs120 and long noncoding RNAs,121 such as TUG1,122, 123 miR-34,124 lincRNA-p21,125 PANDA126 and PINT.127”
From Census and evaluation of p53 target genes (2017) · cites this paper as [122]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Self-citationHigh-Resolution Profiling of Histone Methylations in the Human Genome
Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Schones, D. E., Wang, Z., Wei, G., Chepelev, I., & Zhao, K. (2007) · Cell · doi:10.1016/j.cell.2007.05.009 · Cited by 6,845 · see citing works
The ENCODE Project Consortium (2007) · Nature · doi:10.1038/nature05874 · Cited by 5,223 · see citing works
Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs
Rinn, J. L., Kertesz, M., Wang, J. K., Squazzo, S. L., Xu, X. H., Brugmann, S. A., Goodnough, L. H., Helms, J. A., Farnham, P., Segal, E., et al. (2007) · Cell · doi:10.1016/j.cell.2007.05.022 · Cited by 4,246 · see citing works
Self-citationGenome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129 · see citing works
Self-citationChromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., et al. (2009) · Nature · doi:10.1038/nature07672 · Cited by 4,098 · see citing works
Self-citationPolycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome
Zhao, J. C., Sun, B. K., Erwin, J. A., Song, J., & Lee, J. T. (2008) · Science · doi:10.1126/science.1163045 · Cited by 1,580 · see citing works
Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitionsPreprint
Bracken, A. P., Dietrich, N., Pasini, D., Hansen, K. H., & Helin, K. (2006) · Genes & Development · doi:10.1101/gad.381706 · Cited by 1,258 · see citing works
Pandey, R. R., Mondal, T., Mohammad, F., Enroth, S., Redrup, L., Komorowski, J., Nagano, T., Mancini‐DiNardo, D., & Kanduri, C. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.08.022 · Cited by 1,192 · see citing works
Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains
Ku, M., Koche, R. P., Rheinbay, E., Mendenhall, E. M., Endoh, M., Mikkelsen, T. S., Aiden, A. P., Nusbaum, C., Xie, X. S., Chi, A. S., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000242 · Cited by 996 · see citing works
Self-citationThe Air Noncoding RNA Epigenetically Silences Transcription by Targeting G9a to Chromatin
Nagano, T., Mitchell, J. A., Sanz, L. A., Pauler, F. M., Ferguson‐Smith, A. C., Feil, R., & Fraser, P. (2008) · Science · doi:10.1126/science.1163802 · Cited by 907 · see citing works
Non‐coding RNAs: the architects of eukaryotic complexity
Mattick, J. S. (2001) · EMBO Reports · doi:10.1093/embo-reports/kve230 · Cited by 848 · see citing works
Small RNAs in transcriptional gene silencing and genome defence
Moazed, D. (2009) · Nature · doi:10.1038/nature07756 · Cited by 825 · see citing works
A Strategy for Probing the Function of Noncoding RNAs Finds a Repressor of NFAT
Willingham, A. T., Orth, A. P., Batalov, S., Peters, E. C., Wen, B., Aza‐Blanc, P., Hogenesch, J. B., & Schultz, P. G. (2005) · Science · doi:10.1126/science.1115901 · Cited by 732 · see citing works
Functionality or transcriptional noise? Evidence for selection within long noncoding RNAsPreprint
Ponjavic, J., Ponting, C. P., & Lunter, G. A. (2007) · Genome Research · doi:10.1101/gr.6036807 · Cited by 731 · see citing works
Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiationPreprint
Dinger, M. E., Amaral, P., Mercer, T. R., Pang, K. C., Bruce, S. J., Gardiner, B., Askarian-Amiri, M., Ru, K., Soldà, G., Simons, C., et al. (2008) · Genome Research · doi:10.1101/gr.078378.108 · Cited by 729 · see citing works
The Genetic Signatures of Noncoding RNAs
Mattick, J. S. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000459 · Cited by 704 · see citing works
Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function
Pang, K. C., Frith, M. C., & Mattick, J. S. (2005) · Trends in Genetics · doi:10.1016/j.tig.2005.10.003 · Cited by 653 · see citing works
Maison, C., Bailly, D., Peters, A. H. F. M., Quivy, J., Roche, D. M. J., Taddei, A., Lachner, M., Jenuwein, T., & Almouzni, G. (2002) · Nature Genetics · doi:10.1038/ng843 · Cited by 651 · see citing works
Sunwoo, H., Dinger, M. E., Wilusz, J. E., Amaral, P., Mattick, J. S., & Spector, D. L. (2008) · Genome Research · doi:10.1101/gr.087775.108 · Cited by 649 · see citing works
Distinguishing protein-coding and noncoding genes in the human genome
Clamp, M., Fry, B., Kamal, M., Xie, X., Cuff, J., Lin, M. F., Kellis, M., Lindblad-Toh, K., & Lander, E. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709013104 · Cited by 624 · see citing works
Self-citationCui, K., Zang, C., Roh, T., Schones, D. E., Childs, R. W., Peng, W., & Zhao, K. (2009) · Cell stem cell · doi:10.1016/j.stem.2008.11.011 · Cited by 620 · see citing works
RNA meets chromatinPreprint
Bernstein, E., & Allis, C. D. (2005) · Genes & Development · doi:10.1101/gad.1324305 · Cited by 609 · see citing works
Bernstein, E., Duncan, E. M., Masui, O., Gil, J., Heard, É., & Allis, C. D. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.7.2560-2569.2006 · Cited by 531 · see citing works
The Noncoding RNA Taurine Upregulated Gene 1 Is Required for Differentiation of the Murine Retina
Young‐Pearse, T. L., Matsuda, T., & Cepko, C. L. (2005) · Current Biology · doi:10.1016/j.cub.2005.02.027 · Cited by 500 · see citing works
CoREST: A functional corepressor required for regulation of neural-specific gene expression
Andrés, M. E., Burger, C., Peral-Rubio, M. J., Battaglioli, E., Anderson, M. E., Grimes, J., Dallman, J., Ballas, N., & Mandel, G. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.17.9873 · Cited by 442 · see citing works
Identifying novel constrained elements by exploiting biased substitution patterns
Garber, M., Guttman, M., Clamp, M., Zody, M. C., Friedman, N., & Xie, X. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp190 · Cited by 370 · see citing works
Self-citationAffar, E. B., Gay, F., Shi, Y. G., Liu, H., Huarte, M., Wu, S., Li, E., Li, E., & Shi, Y. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.9.3565-3581.2006 · Cited by 188 · see citing works
Self-citationLin, M. F., Deoras, A., Rasmussen, M. D., & Kellis, M. (2008) · PLoS Comput. Biol. · doi:10.1371/journal.pcbi.1000067 · Cited by 61 · see citing works
Flagged first, then by citations
1 of the 30 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?
Salmena, L., Poliseno, L., Tay, Y., Kats, L., & Pandolfi, P. P. (2011) · Cell · doi:10.1016/j.cell.2011.07.014 · Cited by 7,262 · see citing works
Li, J.-H., Liu, S., Zhou, H., Qu, L., & Yang, J.-H. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1248 · Cited by 5,587 · see citing works
Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis
Gupta, R. A., Shah, N., Wang, K., Kim, J., Horlings, H. M., Wong, D. J., Tsai, M.-C., Hung, T., Argani, P., Rinn, J. L., et al. (2010) · Nature · doi:10.1038/nature08975 · Cited by 5,203 · see citing works
Self-citationDerrien, T., Johnson, R., Bussotti, G., Andrea Tanzer, A., Djebali, S., Tilgner, H., Guernec, G., Martin, D., Merkel, A., Knowles, D. G., et al. (2012) · Genome Research · doi:10.1101/gr.132159.111 · Cited by 5,017 · see citing works
Molecular Mechanisms of Long Noncoding RNAs
Wang, K., & Chang, H. Y. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.018 · Cited by 4,390 · see citing works
Genome Regulation by Long Noncoding RNAs
Rinn, J. L., & Chang, H. Y. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-051410-092902 · Cited by 4,011 · see citing works
Self-citationUnique features of long non-coding RNA biogenesis and function
Quinn, J. J., & Chang, H. Y. (2015) · Nature Reviews Genetics · doi:10.1038/nrg.2015.10 · Cited by 3,653 · see citing works
Cabili, M. N., Trapnell, C., Goff, L. A., Koziol, M. J., Tazón‐Vega, B., Regev, A., & Rinn, J. L. (2011) · Genes & Development · doi:10.1101/gad.17446611 · Cited by 3,473 · see citing works
Self-citationThe Polycomb complex PRC2 and its mark in life
Margueron, R., & Reinberg, D. (2011) · Nature · doi:10.1038/nature09784 · Cited by 3,347 · see citing works
Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes
Tsai, M.-C., Manor, O., Wan, Y., Mosammaparast, N., Wang, J. K., Lan, F., Shi, Y., Segal, E., & Chang, H. Y. (2010) · Science · doi:10.1126/science.1192002 · Cited by 3,290 · see citing works
Long non-coding RNAs: new players in cell differentiation and development
Fatica, A., & Bozzoni, I. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3606 · Cited by 2,980 · see citing works
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
Spatial partitioning of the regulatory landscape of the X-inactivation centre
Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N. L., Meisig, J., Sedat, J., et al. (2012) · Nature · doi:10.1038/nature11049 · Cited by 2,895 · see citing works
Long Noncoding RNA and Cancer: A New Paradigm
Bhan, A., Soleimani, M., & Mandal, S. S. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2634 · Cited by 2,868 · see citing works
Epigenetic modifications and human disease
Portela, A., & Esteller, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1685 · Cited by 2,843 · see citing works
The emerging role of lncRNAs in cancer
Huarte, M. (2015) · Nature Medicine · doi:10.1038/nm.3981 · Cited by 2,686 · see citing works
Self-citationGenetics and pathogenesis of inflammatory bowel disease
Khor, B., Gardet, A., & Xavier, R. J. (2011) · Nature · doi:10.1038/nature10209 · Cited by 2,630 · see citing works
lincRNAs: Genomics, Evolution, and Mechanisms
Ulitsky, I., & Bartel, D. P. (2013) · Cell · doi:10.1016/j.cell.2013.06.020 · Cited by 2,596 · see citing works
An atlas of active enhancers across human cell types and tissues
The FANTOM Consortium, Andersson, R., Gebhard, C., Miguel-Escalada, I., Hoof, I., Bornholdt, J., Boyd, M., Chen, Y., Zhao, X., Schmidl, C., et al. (2014) · Nature · doi:10.1038/nature12787 · Cited by 2,550 · see citing works
Long Noncoding RNAs: Cellular Address Codes in Development and Disease
Batista, P. J., & Chang, H. Y. (2013) · Cell · doi:10.1016/j.cell.2013.02.012 · Cited by 2,531 · see citing works
The Noncoding RNA Revolution—Trashing Old Rules to Forge New Ones
Cech, T. R., & Steitz, J. A. (2014) · Cell · doi:10.1016/j.cell.2014.03.008 · Cited by 2,270 · see citing works
Long non-coding RNAs: definitions, functions, challenges and recommendations
Mattick, J. S., Amaral, P., Carninci, P., Carpenter, S. B., Chang, H. Y., Chen, L., Chen, R., Dean, C., Dinger, M. E., Fitzgerald, K. A., et al. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00566-8 · Cited by 2,416 · see citing works
Self-citationModular regulatory principles of large non-coding RNAs
Guttman, M., & Rinn, J. L. (2012) · Nature · doi:10.1038/nature10887 · Cited by 2,257 · see citing works
Self-citationCircular intronic long noncoding RNAs
Zhang, Y., Zhang, X.-O., Chen, T., Xiang, J.-F., Yin, Q.-F., Xing, Y.-H., Zhu, S., Yang, L., & Chen, L.-L. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.017 · Cited by 2,221 · see citing works
Ingolia, N. T., Lareau, L. F., & Weissman, J. S. (2011) · Cell · doi:10.1016/j.cell.2011.10.002 · Cited by 2,187 · see citing works
A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response
Huarte, M., Guttman, M., Feldser, D., Garber, M., Koziol, M. J., Kenzelmann-Broz, D., Khalil, A. M., Zuk, O., Amit, I., Rabani, M., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.040 · Cited by 2,053 · see citing works
Self-citationLong noncoding RNAs: past, present, and future
Kung, J. T. Y., Colognori, D., & Lee, J. T. (2013) · Genetics · doi:10.1534/genetics.112.146704 · Cited by 1,874 · see citing works
Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells
Yan, L., Yang, M., Guo, H., Yang, L., Wu, J., Li, R., Liu, P., Lian, Y., Zheng, X., Yan, J., et al. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2660 · Cited by 1,740 · see citing works
lincRNAs act in the circuitry controlling pluripotency and differentiation
Guttman, M., Donaghey, J., Carey, B. W., Garber, M. G., Grenier, J. K., Munson, G., Young, G., Lucas, A. B., Ach, R. A., Bruhn, L., et al. (2011) · Nature · doi:10.1038/nature10398 · Cited by 1,845 · see citing works
Self-citationGutschner, T., & Diederichs, S. (2012) · RNA Biology · doi:10.4161/rna.20481 · Cited by 1,803 · see citing works
The Emergence of lncRNAs in Cancer Biology
Prensner, J. R., & Chinnaiyan, A. M. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0209 · Cited by 1,761 · see citing works
Long Noncoding RNAs with Enhancer-like Function in Human Cells
Ørom, U. A., Derrien, T., Beringer, M., Gumireddy, K., Gardini, A., Bussotti, G., Lai, F., Zytnicki, M., Notredame, C., Huang, Q., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.001 · Cited by 1,721 · see citing works
Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches
Beermann, J., Piccoli, M.-T., Viereck, J., & Thum, T. (2016) · Physiological Reviews · doi:10.1152/physrev.00041.2015 · Cited by 1,727 · see citing works
The functional role of long non-coding RNA in human carcinomas
Gibb, E. A., Brown, C. J., & Lam, W. L. (2011) · Molecular Cancer · doi:10.1186/1476-4598-10-38 · Cited by 1,615 · see citing works
LNCcation: lncRNA localization and function
Bridges, M. C., Daulagala, A. C., & Kourtidis, A. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202009045 · Cited by 1,556 · see citing works
MicroRNAs and other non-coding RNAs as targets for anticancer drug development
Ling, H. Y., Fabbri, M., & Călin, G. A. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4140 · Cited by 1,465 · see citing works
RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts
Geisler, S., & Coller, J. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3679 · Cited by 1,451 · see citing works
Mechanisms of stress in the brain
McEwen, B. S., Bowles, N. P., Gray, J. D., Hill, M. N., Hunter, R. G., Karatsoreos, I. N., & Nasca, C. (2015) · Nature Neuroscience · doi:10.1038/nn.4086 · Cited by 1,386 · see citing works
Structure and function of long noncoding RNAs in epigenetic regulation
Mercer, T. R., & Mattick, J. S. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2480 · Cited by 1,436 · see citing works
Yap, K. L., Li, S., Muñoz-Cabello, A. M., Raguz, S., Zeng, L., Mujtaba, S., Gil, J., Walsh, M. J., & Zhou, M.-M. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.03.021 · Cited by 1,391 · see citing works
Morris, K. V., & Mattick, J. S. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3722 · Cited by 1,389 · see citing works
High-Throughput Sequencing Technologies
Reuter, J., Spacek, D. V., & Snyder, M. P. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.05.004 · Cited by 1,330 · see citing works
The functions and unique features of long intergenic non-coding RNA
Ransohoff, J. D., Wei, Y., & Khavari, P. A. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.104 · Cited by 1,337 · see citing works
On the classification of long non-coding RNAs
Ma, L., Bajić, V. B., & Zhang, Z. (2013) · RNA Biology · doi:10.4161/rna.24604 · Cited by 1,333 · see citing works
Guttman, M., Garber, M., Levin, J. Z., Donaghey, J., Robinson, J., Adiconis, X., Fan, L., Koziol, M. J., Gnirke, A., Nusbaum, C., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1633 · Cited by 1,253 · see citing works
Self-citationGenomic Maps of Long Noncoding RNA Occupancy Reveal Principles of RNA-Chromatin Interactions
Chu, C., Qu, K., Zhong, F. L., Artandi, S. E., & Chang, H. Y. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.027 · Cited by 1,274 · see citing works
Epigenetic Regulation by Long Noncoding RNAs
Lee, J. T. (2012) · Science · doi:10.1126/science.1231776 · Cited by 1,258 · see citing works
Kogo, R., Shimamura, T., Mimori, K., Kawahara, K., Imoto, S., Sudo, T., Tanaka, F., Shibata, K., Suzuki, A., Komune, S., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1021 · Cited by 1,238 · see citing works
The Landscape of long noncoding RNA classification
Laurent, G. S., Wahlestedt, C., & Kapranov, P. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.03.007 · Cited by 1,192 · see citing works
Epigenetics and gene expression
Gibney, E. R., & Nolan, C. M. (2010) · Heredity · doi:10.1038/hdy.2010.54 · Cited by 1,109 · see citing works
Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution
Ulitsky, I., Shkumatava, A., Jan, C. H., Sive, H. L., & Bartel, D. P. (2011) · Cell · doi:10.1016/j.cell.2011.11.055 · Cited by 1,162 · see citing works
Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters
Hung, T., Wang, Y., Lin, M. F., Koegel, A. K., Kotake, Y., Grant, G. D., Horlings, H. M., Shah, N., Umbricht, C. B., Wang, P., et al. (2011) · Nature Genetics · doi:10.1038/ng.848 · Cited by 1,165 · see citing works
Mechanisms of long noncoding RNA function in development and disease
Schmitz, S. U., Grote, P., & Herrmann, B. G. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2174-5 · Cited by 1,088 · see citing works
Gene co-expression analysis for functional classification and gene–disease predictions
van Dam, S., Võsa, U., van der Graaf, A., Franke, L., & de Magalhães, J. P. (2017) · Briefings in Bioinformatics · doi:10.1093/bib/bbw139 · Cited by 1,086 · see citing works
Roles, Functions, and Mechanisms of Long Non-Coding RNAs in Cancer
Fang, Y., & Fullwood, M. J. (2016) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2015.09.006 · Cited by 1,068 · see citing works
Non‐coding RNAs: regulators of disease
Taft, R. J., Pang, K. C., Mercer, T. R., Dinger, M. E., & Mattick, J. S. (2009) · The Journal of Pathology · doi:10.1002/path.2638 · Cited by 1,056 · see citing works
Linking Long Noncoding RNA Localization and Function
Chen, L. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.07.003 · Cited by 1,042 · see citing works
Census and evaluation of p53 target genes
Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971 · see citing works
Non-coding RNAs as drug targets
Matsui, M., & Corey, D. R. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.117 · Cited by 1,036 · see citing works
Long non-coding RNAs and cancer: a new frontier of translational research?
Spizzo, R., Almeida, M. I., Colombatti, A., & Călin, G. A. (2012) · Oncogene · doi:10.1038/onc.2011.621 · Cited by 1,004 · see citing works
LncRNA: A link between RNA and cancer
Yang, G., Lu, X., & Yuan, L. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.08.012 · Cited by 992 · see citing works
The evolution of lncRNA repertoires and expression patterns in tetrapods
Necsulea, A., Soumillon, M., Warnefors, M., Liechti, A., Daish, T., Zeller, U., Baker, J. C., Grützner, F., & Kaessmann, H. (2014) · Nature · doi:10.1038/nature12943 · Cited by 984 · see citing works
Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells
Loewer, S., Cabili, M. N., Guttman, M., Loh, Y., Thomas, K., Park, I. H., Garber, M. G., Curran, M. S., Önder, T. T., Agarwal, S., et al. (2010) · Nature Genetics · doi:10.1038/ng.710 · Cited by 971 · see citing works
Self-citationGenome-wide Identification of Polycomb-Associated RNAs by RIP-seq
Zhao, J. C., Ohsumi, T. K., Kung, J. T., Ogawa, Y., Grau, D., Sarma, K., Song, J. J., Kingston, R. E., Borowsky, M. L., & Lee, J. T. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.12.011 · Cited by 974 · see citing works
Grote, P., Wittler, L., Hendrix, D. A., Koch, F., Währisch, S., Beisaw, A., Macura, K., Bläß, G., Kellis, M., Werber, M., et al. (2013) · Developmental Cell · doi:10.1016/j.devcel.2012.12.012 · Cited by 977 · see citing works
The multidimensional mechanisms of long noncoding RNA function
Marchese, F. P., Raimondi, I., & Huarte, M. (2017) · Genome biology · doi:10.1186/s13059-017-1348-2 · Cited by 966 · see citing works
Self-citationNon-coding RNAs: Classification, Biology and Functioning
Hombach, S., & Kretz, M. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-42059-2_1 · Cited by 959 · see citing works
A Long Noncoding RNA Mediates Both Activation and Repression of Immune Response Genes
Carpenter, S. B., Aiello, D. A., Atianand, M., Ricci, E. P., Gandhi, P., Hall, L. L., Byron, M., Monks, B. G., Henry-Bezy, M., Lawrence, J. B., et al. (2013) · Science · doi:10.1126/science.1240925 · Cited by 946 · see citing works
Control of somatic tissue differentiation by the long non-coding RNA TINCR
Kretz, M., Siprashvili, Z., Chu, C., Webster, D., Zehnder, A., Qu, K., Lee, C. S., Flockhart, R., Groff, A., Chow, J. M., et al. (2012) · Nature · doi:10.1038/nature11661 · Cited by 920 · see citing works
Self-citationLiu, X.-H., Sun, M., 聂凤琪, Ge, Y.-B., Zhang, E., Yin, D., Kong, R., Xia, R., Lu, K., Li, J.-H., et al. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-92 · Cited by 946 · see citing works
Transcriptional and Post-Transcriptional Gene Regulation by Long Non-Coding RNA
Dykes, I. M., & Emanueli, C. (2017) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.12.005 · Cited by 909 · see citing works
Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment
Klattenhoff, C., Scheuermann, J. C., Surface, L. E., Bradley, R. K., Fields, P., Steinhauser, M. L., Ding, H., Butty, V. L., Sosa, L. T., Haas, S. F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.003 · Cited by 910 · see citing works
Non-coding RNA: what is functional and what is junk?
Palazzo, A. F., & Lee, E. S. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00002 · Cited by 891 · see citing works
No-Nonsense Functions for Long Noncoding RNAs
Nagano, T., & Fraser, P. (2011) · Cell · doi:10.1016/j.cell.2011.03.014 · Cited by 877 · see citing works
History, Discovery, and Classification of lncRNAs
Jarroux, J., Morillon, A., & Pinskaya, M. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-5203-3_1 · Cited by 873 · see citing works
Fujimoto, A., Totoki, Y., Abe, T., Boroevich, K. A., Hosoda, F., Hà, N. H., Aoki, M., Hosono, N., Kubo, M., Miya, F., et al. (2012) · Nature Genetics · doi:10.1038/ng.2291 · Cited by 868 · see citing works
Transcriptional regulation by Polycomb group proteins
Di Croce, L., & Helin, K. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2669 · Cited by 864 · see citing works
The Hox genes and their roles in oncogenesis
Shah, N., & Sukumar, S. V. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2826 · Cited by 832 · see citing works
The complex transcriptional landscape of the anucleate human platelet
Bray, P. F., McKenzie, S. E., Edelstein, L. C., Nagalla, S., Delgrosso, K., Ertel, A., Kupper, J., Jing, Y., Londin, E., Loher, P., et al. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-1 · Cited by 802 · see citing works
Long Non-Coding RNA in the Pathogenesis of Cancers
Chi, Y., Wang, D., Wang, J., Yu, W., & Yang, J. (2019) · Cells · doi:10.3390/cells8091015 · Cited by 780 · see citing works
Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesisPreprint
Pauli, A., Valen, E., Lin, M. F., Garber, M. G., Vastenhouw, N. L., Levin, J. Z., Fan, L., Sandelin, A., Rinn, J. L., Regev, A., et al. (2011) · Genome Research · doi:10.1101/gr.133009.111 · Cited by 776 · see citing works
Self-citationWang, Y., Xu, Z., Jiang, J., Xu, C., Kang, J., Xiao, L., Wu, M., Xiong, J., Guo, X., & Liu, H. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.03.002 · Cited by 784 · see citing works
HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer
Kim, K., Jutooru, I., Chadalapaka, G., Johnson, G. A., Frank, J., Burghardt, R. C., Kim, S., & Safe, S. H. (2012) · Oncogene · doi:10.1038/onc.2012.193 · Cited by 781 · see citing works
Non-coding RNAs as regulators of gene expression and epigenetics
Kaikkonen, M. U., Lam, M. T. Y., & Glass, C. K. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr097 · Cited by 764 · see citing works
Chromatin structure and the inheritance of epigenetic information
Margueron, R., & Reinberg, D. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2752 · Cited by 733 · see citing works
Hangauer, M. J., Vaughn, I. W., & McManus, M. T. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003569 · Cited by 738 · see citing works
A long nuclear‐retained non‐coding RNA regulates synaptogenesis by modulating gene expression
Bernard, D., Prasanth, K. V., Tripathi, V., Colasse, S., Nakamura, T., Xuan, Z., Zhang, M. Q., Sedel, F., Jourdren, L., Coulpier, F., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.199 · Cited by 738 · see citing works
Simon, J. A., & Kingston, R. E. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.02.013 · Cited by 727 · see citing works
Regulation of gene expression by cis-acting long non-coding RNAs
Gil, N., & Ulitsky, I. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0184-5 · Cited by 712 · see citing works
Long noncoding RNAs and the genetics of cancer
Cheetham, S. W., Gruhl, F., Mattick, J. S., & Dinger, M. E. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.233 · Cited by 724 · see citing works
Yang, Z., Zhou, L., Wu, L., Lai, M.-C., Xie, H., Zhang, F., & Zheng, S. (2011) · Annals of Surgical Oncology · doi:10.1245/s10434-011-1581-y · Cited by 709 · see citing works
Genome-Wide Analysis Uncovers Regulation of Long Intergenic Noncoding RNAs in Arabidopsis
Liu, J., Jung, C., Xu, J. Q., Wang, H., Deng, S., Bernad, L., Arenas‐Huertero, C., & Chua, N. (2012) · The Plant Cell · doi:10.1105/tpc.112.102855 · Cited by 693 · see citing works
Peptidomic discovery of short open reading frame–encoded peptides in human cells
Slavoff, S. A., Mitchell, A. J., Schwaid, A. G., Cabili, M. N., Ma, J., Levin, J. Z., Karger, A., Budnik, B., Rinn, J. L., & Saghatelian, A. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1120 · Cited by 678 · see citing works
Self-citationKapusta, A., Kronenberg, Z., Lynch, V. J., Zhuo, X., Ramsay, L., Bourque, G., Yandell, M., & Feschotte, C. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003470 · Cited by 687 · see citing works
Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution
Cabili, M. N., Dunagin, M. C., McClanahan, P. D., Biaesch, A. G., Padovan-Merhar, O. M., Regev, A., Rinn, J. L., & Raj, A. (2015) · Genome biology · doi:10.1186/s13059-015-0586-4 · Cited by 684 · see citing works
Self-citationMultiple knockout mouse models reveal lincRNAs are required for life and brain development
Sauvageau, M., Goff, L. A., Lodato, S., Bonev, B., Groff, A. F., Gerhardinger, C., Sanchez-Gomez, D. B., Hacisuleyman, E., Li, E. V., Spence, M. C., et al. (2013) · eLife · doi:10.7554/elife.01749 · Cited by 675 · see citing works
Self-citationPolycomb Group Proteins: Multi-Faceted Regulators of Somatic Stem Cells and Cancer
Sauvageau, M., & Sauvageau, G. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.08.002 · Cited by 676 · see citing works
Bazzini, A., Johnstone, T. G., Christiano, R., Mackowiak, S. D., Obermayer, B., Fleming, E. S., Vejnar, C. E., Lee, M. T., Rajewsky, N., Walther, T. C., et al. (2014) · The EMBO Journal · doi:10.1002/embj.201488411 · Cited by 657 · see citing works
Mondal, T., Subhash, S., Vaid, R., Enroth, S., Uday, S., Reinius, B., Mitra, S., Mohammed, A., James, A. R., Hoberg, E., et al. (2015) · Nature Communications · doi:10.1038/ncomms8743 · Cited by 665 · see citing works
Long Noncoding RNA in Prostate, Bladder, and Kidney Cancer
Martens‐Uzunova, E. S., Böttcher, R., Croce, C. M., Jenster, G. W., Visakorpi, T., & Călin, G. A. (2013) · European Urology · doi:10.1016/j.eururo.2013.12.003 · Cited by 656 · see citing works
- Authors
- Khalil, A. M., Guttman, M., Huarte, M., Garber, M., Raj, A., Rivea Morales, D., Thomas, K., Presser, A., Bernstein, B. E., van Oudenaarden, A., Regev, A., Lander, E. S., & Rinn, J. L.
- Affiliations
- Broad Institute (US)
- Massachusetts Institute of Technology (US)
- The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
- Physics, Massachusetts Institute of Technology, Cambridge, MA 02139;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-07-14
- Volume
- 106
- Issue
- 28
- Pages
- 11667-11672
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2704857
- OpenAlex
- W2144137532
- Cited by
- 2,872
- References
- 30
- Citations by year
- 2026: 35 · 2025: 54 · 2024: 81 · 2023: 96 · 2022: 115 · 2021: 164 · 2020: 206 · 2019: 208 · 2018: 216 · 2017: 230 · 2016: 235 · 2015: 269 · 2014: 248 · 2013: 243 · 2012: 197
- FWCI
- 52.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (DP1OD003958)
- National Heart, Lung, and Blood Institute (T32HL007893, HL007893)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- long intergenic non-coding RNA, polycomb repressive complex 2, chromatin-modifying complexes, gene expression regulation, HOTAIR, chromatin state, siRNA knockdown, gene silencing, mammalian genomes
- MeSH terms
- Chromatin, Gene Expression Regulation, Humans, Models, Genetic, Repressor Proteins, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, RNA, Untranslated, Epigenesis, Genetic, Polycomb-Group Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
