Cited by 4,098Cancer-related molecular mechanisms researchGenomics and Chromatin DynamicsChromosomal and Genetic Variations

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals

Open access

Guttman, Mitchell, Amit, Ido, Garber, Manuel, French, Courtney, Lin, Michael F., Feldser, David, Huarte, Maite, Zuk, Or, Carey, Bryce W., Cassady, John P., Cabili, Moran N., Jaenisch, Rudolf, Mikkelsen, Tarjei S., Jacks, Tyler, Hacohen, Nir, Bernstein, Bradley E., Kellis, Manolis, Regev, Aviv, Rinn, John L., Lander, Eric S.·2009·Nature

DOI 10.1038/nature07672PMC PMC2754849

Open this paper in CoChat — free account

Abstract

There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise. Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified approximately 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFkappaB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.

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

Crossref · 10.1038/nature07672

Cites

39 of 39 references verified0 citation errors · 0 not checkable

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
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
Self-citation
High-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
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
Self-citation
Genome-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
Self-citation
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., et al. (2005) · Genome Research · doi:10.1101/gr.3715005 · Cited by 3,971
miRBase: microRNA sequences, targets and gene nomenclature
Griffiths-Jones, S. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj112 · Cited by 3,950
The Transcriptional Landscape of the Mammalian Genome
Carninci, P., Kasukawa, T., Katayama, S., Gough, J., Frith, M. C., Maeda, N., Oyama, R., Ravasi, T., Lenhard, B., Wells, C. A., et al. (2005) · Science · doi:10.1126/science.1112014 · Cited by 3,492 · cited 2×
“Thus, to expand our understanding of functional lincRNAs, we are faced with two important challenges: (1) identifying lincRNAs that are most likely to be functional; and (2) inferring putative functions for these lincRNAs that can be tested in hypothesis-driven experiments.”
RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription
Kapranov, P., Cheng, J., Dike, S., Nix, D. A., Duttagupta, R., Willingham, A. T., Stadler, P. F., Jana Hertel, A., Jörg Hackermüller, A., Hofacker, I. L., et al. (2007) · Science · doi:10.1126/science.1138341 · Cited by 2,519 · cited 1×
“(1) Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge MA 02142 (2) Department of Biology, Massachusetts Institute of Technology, Cambridge MA 02139 (3) Department of Pathology, Beth Israel Deaconess Medical Center, Boston MA 02215 (4) Division of Health Sciences and Technology, Massachusetts Institute…”
The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells
Loh, Y., Wu, Q., Chew, J.-L., Vega, V. B., Zhang, W., Chen, X., Bourque, G., George, J., Leong, B., Liu, J., et al. (2006) · Nature Genetics · doi:10.1038/ng1760 · Cited by 2,438
Identification of protein coding regions by database similarity search
Gish, W. R., & States, D. J. (1993) · Nature Genetics · doi:10.1038/ng0393-266 · Cited by 1,650

Flagged first, then by citations

Show all 39 references

Sorted by citations

Items 801–900 of 1,007

The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis
Qiu, J., Wang, Y., Ding, J., Jin, H., Yang, G. S., & Hua, K. (2015) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.03.005 · Cited by 102
AS1DHRS4, a head-to-head natural antisense transcript, silences the DHRS4 gene cluster in cis and trans
Li, Q., Su, Z., Xu, X., Liu, G., Song, X., Wang, R., Sui, X., Liu, T., Chang, X., & Huang, D. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116597109 · Cited by 102
Systematic identification and characterization of long intergenic non-coding RNAs in fetal porcine skeletal muscle development
Zhao, W., Mu, Y., Ma, L., Wang, C., Tang, Z., Yang, S., Zhou, R., Hu, X., Li, M.-H., & Li, K. (2015) · Scientific Reports · doi:10.1038/srep08957 · Cited by 101
MicroRNA-23b Targets Ras GTPase-Activating Protein SH3 Domain-Binding Protein 2 to Alleviate Fibrosis and Albuminuria in Diabetic Nephropathy
Zhao, B., Li, H., Liu, J., Han, P., Zhang, C., Bai, H., Yuan, X., Wang, X., Li, L., Ma, H., et al. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015030300 · Cited by 102
FMLNCSIM: fuzzy measure-based lncRNA functional similarity calculation model
Chen, X., Huang, Y., Wang, X., You, Z., & Chan, K. C. C. (2016) · Oncotarget · doi:10.18632/oncotarget.10008 · Cited by 103
HLPI-Ensemble: Prediction of human lncRNA-protein interactions based on ensemble strategy
Hu, H., Zhang, L., Ai, H., Zhang, H., Fan, Y., Zhao, Q., & Liu, H. (2018) · RNA Biology · doi:10.1080/15476286.2018.1457935 · Cited by 101
“For example, regulation of gene expression [2], transcription and post-translational regulation [3], chromatin modi ﬁ cation [4,5], disease progression [6] and development [7 – 10].”
Background
Long non-coding RNAs: Functional regulatory players in breast cancer
Youness, R. A., & Gad, M. Z. (2019) · Non-coding RNA Research · doi:10.1016/j.ncrna.2019.01.003 · Cited by 102
“The total number of lncRNAs continues to ascend, catalyzed by deeper and more sensitive RNA sequencing techniques, improved epigenomic technologies and computational prediction techniques [27,28].”
Background
Non-coding RNAs: Epigenetic regulators of bone development and homeostasis
Hassan, M. Q., Tye, C. E., Stein, G. S., & Lian, J. B. (2015) · Bone · doi:10.1016/j.bone.2015.05.026 · Cited by 102
Long non-coding RNAs in innate and adaptive immunity
Aune, T. M., & Spurlock, C. F. (2015) · Virus Research · doi:10.1016/j.virusres.2015.07.003 · Cited by 105
Epigenetic Modifications in the Pathogenesis of Diabetic Nephropathy
Reddy, M. A., Park, J. T., & Natarajan, R. D. (2013) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2013.05.006 · Cited by 100
Biomarker discovery: quantification of microRNAs and other small non-coding RNAs using next generation sequencing
López, J. P., Diallo, A., Cruceanu, C., Fiori, L. M., LaBoissière, S., Guillet, I., Fontaine, J., Ragoussis, J., Beneš, V., Turecki, G., et al. (2015) · BMC Medical Genomics · doi:10.1186/s12920-015-0109-x · Cited by 106
Long non‐coding RNA: A new paradigm for lung cancer
Khandelwal, A., Bacolla, A., Vásquez, K. M., & Jain, A. (2015) · Molecular Carcinogenesis · doi:10.1002/mc.22362 · Cited by 102
Dynamic Expression of Long Non-Coding RNAs (lncRNAs) in Adult Zebrafish
Kaushik, K., Leonard, V. E., Vellarikkal, S. K., Lalwani, M. K., Jalali, S., Patowary, A., Joshi, A., Scaria, V., & Sivasubbu, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083616 · Cited by 101
Transcriptional and epigenetic regulation of the p53 tumor suppressor gene
Saldaña-Meyer, R., & Targa, F. R. (2011) · Epigenetics · doi:10.4161/epi.6.9.16683 · Cited by 103
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 103
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 100
Long noncoding RNA #32 contributes to antiviral responses by controlling interferon-stimulated gene expression
Nishitsuji, H., Ujino, S., Yoshio, S., Sugiyama, M., Mizokami, M., Kanto, T., & Shimotohno, K. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525022113 · Cited by 100
“Most lncRNAs, as well as protein-coding mRNAs, are capped, polyadenylated, and spliced by cellular machinery (7).”
Background
LncRNA MALAT1 promotes development of mantle cell lymphoma by associating with EZH2
Wang, X., Sehgal, L., Jain, N. K., Khashab, T., Mathur, R., & Samaniego, F. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-1100-9 · Cited by 101
“It has been demonstrated that lncRNAs influence tumor progression through modulating cell cycle, survival, immune response or pluripotency, through their interactions with DNA, protein, and RNA [6, 7].”
Background
Potential Implications of Long Noncoding RNAs in Autoimmune Diseases
Hur, K., Kim, S.-H., & Kim, J. (2019) · Immune Network · doi:10.4110/in.2019.19.e4 · Cited by 99
Emerging Roles for Long Non-Coding RNAs in Cancer and Neurological Disorders
Niland, C. N., Merry, C. R., & Khalil, A. M. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00025 · Cited by 103
Involvement of long noncoding RNAs in diseases affecting the central nervous system
Pastori, C., & Wahlestedt, C. (2012) · RNA Biology · doi:10.4161/rna.20482 · Cited by 100
Long Noncoding RNA Expression during Human B-Cell Development
Petri, A., Dybkær, K., Bøgsted, M., Thrue, C. A., Hagedorn, P., Schmitz, A., Bødker, J. S., Johnsen, H. E., & Kauppinen, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138236 · Cited by 105
The Epigenetic Landscape of Mammary Gland Development and Functional Differentiation
Rijnkels, M., Kabotyanski, E. B., Montazer-Torbati, M. B., Hue-Beauvais, C., Vassetzky, Y. S., Rosen, J. M., & Devinoy, È. (2010) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-010-9170-4 · Cited by 104
Expression and diversification analysis reveals transposable elements play important roles in the origin of L ycopersicon‐specific lnc RNA s in tomato
Wang, X., Ai, G., Zhang, C., Cui, L., Wang, J., Li, J., Zhang, J., & Ye, Z. (2015) · New Phytologist · doi:10.1111/nph.13718 · Cited by 100
Long non-coding RNA MALAT-1 is downregulated in preeclampsia and regulates proliferation, apoptosis, migration and invasion of JEG-3 trophoblast cells.
Chen, H., Meng, T., Liu, X., Sun, M., Tong, C., Liu, J., Wang, H., & Du, J. (2015) · PubMed Central · Cited by 100
Long non-coding RNA FEZF1-AS1 facilitates cell proliferation and migration in colorectal carcinoma
Chen, N., Guo, D., Xu, Q., Yang, M., Wang, D., Peng, M., Ding, Y., Wang, S., & Zhou, J. (2016) · Oncotarget · doi:10.18632/oncotarget.7168 · Cited by 100
Transcriptome Analysis Reveals Distinct Gene Expression Profiles in Eosinophilic and Noneosinophilic Chronic Rhinosinusitis with Nasal Polyps
Wang, W., Gao, Z., Wang, H., Li, T., He, W., Lv, W., & Zhang, J. (2016) · Scientific Reports · doi:10.1038/srep26604 · Cited by 101
LncRNA-miRNA axis in tumor progression and therapy response: An emphasis on molecular interactions and therapeutic interventions
Entezari, M., Taheriazam, A., Orouei, S., Fallah, S., Sanaei, A., Hejazi, E. S., Kakavand, A., Rezaei, S., Heidari, H., Behroozaghdam, M., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113609 · Cited by 101
Non-coding RNAs in homeostasis, disease and stress responses: an evolutionary perspective
Amaral, P., Dinger, M. E., & Mattick, J. S. (2013) · Briefings in Functional Genomics · doi:10.1093/bfgp/elt016 · Cited by 103
Comparison of splice sites reveals that long noncoding RNAs are evolutionarily well conserved
Nitsche, A., Rose, D., Fasold, M., Reiche, K., & Stadler, P. F. (2015) · RNA · doi:10.1261/rna.046342.114 · Cited by 99
Pan-cancer transcriptome analysis reveals long noncoding RNAs with conserved function
Cabanski, C. R., White, N. M. A., Dang, H. X., Silva-Fisher, J., Rauck, C. E., Cicka, D., & Maher, C. A. (2015) · RNA Biology · doi:10.1080/15476286.2015.1038012 · Cited by 94
Upregulation of long noncoding RNA TUG1 promotes cervical cancer cell proliferation and migration
Hu, Y., Sun, X., Mao, C., Guo, G., Ye, S., Xu, J., Zou, R., Chen, J., Wang, L., Duan, P., et al. (2017) · Cancer Medicine · doi:10.1002/cam4.994 · Cited by 101
“A large number of studies have shown that mammalian genomes encode thousands of lncRNAs [6].”
Background
A milieu of regulatory elements in the epidermal differentiation complex syntenic block: implications for atopic dermatitis and psoriasis
Strong, C. D. G., Conlan, S., Deming, C., Cheng, J., Sears, K. E., & Segre, J. A. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq019 · Cited by 101
Transcriptional regulation of cellular senescence
Lanigan, F., Geraghty, J. G., & Bracken, A. P. (2011) · Oncogene · doi:10.1038/onc.2011.34 · Cited by 95
Reactome pathway analysis to enrich biological discovery in proteomics data sets
Haw, R., Hermjakob, H., D'Eustachio, P., & Stein, L. (2011) · PROTEOMICS · doi:10.1002/pmic.201100066 · Cited by 117
Long noncoding RNAs and atherosclerosis
Zhou, T., Ding, J., Wang, X., & Zheng, X. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.02.025 · Cited by 98
Functional polymorphism of lncRNA MALAT1 contributes to pulmonary arterial hypertension susceptibility in Chinese people
Zhuo, Y., Zeng, Q., Zhang, P., Li, G., Xie, Q., & Cheng, Y. (2016) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2016-0056 · Cited by 98
The Role of Long Noncoding RNAs in Central Nervous System and Neurodegenerative Diseases
Wei, C.-W., Luo, T., Zou, S.-S., & Wu, A. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00175 · Cited by 104
Identification and functional prediction of cold-related long non-coding RNA (lncRNA) in grapevine
Wang, P., Dai, L., Ai, J., Wang, Y., & Ren, F. (2019) · Scientific Reports · doi:10.1038/s41598-019-43269-5 · Cited by 98
MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression
Chang, K.-C., Diermeier, S. D., Yu, A. T., Brine, L., Russo, S., Bhatia, S., Alsudani, H., Kostroff, K. M., Bhuiya, T. A., Brogi, E., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-20207-y · Cited by 98
Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular Disease
Aguiló, F., Cecilia, S. D., & Walsh, M. J. (2015) · Current topics in microbiology and immunology · doi:10.1007/82_2015_455 · Cited by 99
Long non-coding RNA-mediated transcriptional interference of a permease gene confers drug tolerance in fission yeast
Ard, R., Tong, P., & Allshire, R. C. (2014) · Nature Communications · doi:10.1038/ncomms6576 · Cited by 98
Genome-wide Long Non-coding RNA Analysis Identified Circulating LncRNAs as Novel Non-invasive Diagnostic Biomarkers for Gynecological Disease
Wang, W.-T., Sun, Y.-M., Huang, W., He, B., Zhao, Y.-N., & Chen, Y.-Q. (2016) · Scientific Reports · doi:10.1038/srep23343 · Cited by 97
Cotranscriptional histone H2B monoubiquitylation is tightly coupled with RNA polymerase II elongation rate
Fuchs, G., Hollander, D., Voichek, Y., Ast, G., & Oren, M. (2014) · Genome Research · doi:10.1101/gr.176487.114 · Cited by 102
SNHG3 correlates with malignant status and poor prognosis in hepatocellular carcinoma
Zhang, T., Cao, C., Wu, D., & Liu, L. (2015) · Tumor Biology · doi:10.1007/s13277-015-4052-4 · Cited by 97
Differential expression of long non-coding RNAs during genotoxic stress-induced apoptosis in HeLa and MCF-7 cells
Özgür, E., Mert, U., Işın, M., Okutan, M., Dalay, N., & Deligezer, U. (2012) · Clinical and Experimental Medicine · doi:10.1007/s10238-012-0181-x · Cited by 97
Long noncoding RNAs and prostate carcinogenesis: the missing ‘linc’?
Walsh, A. L., Tuzova, A. V., Bolton, E. M., Lynch, T. H., & Perry, A. S. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.03.005 · Cited by 101
ncRAN, a Newly Identified Long Noncoding RNA, Enhances Human Bladder Tumor Growth, Invasion, and Survival
Zhu, Y., Yu, M., Li, Z., Kong, C., Bi, J., Li, J., Gao, Z., & Li, Z. (2010) · Urology · doi:10.1016/j.urology.2010.09.022 · Cited by 97
The roles of non-coding RNAs in Parkinson’s disease
Majidinia, M., Mihanfar, A., Rahbarghazi‬, R., Nourazarian, A., Bağca, B. G., & Avcı, Ç. B. (2016) · Molecular Biology Reports · doi:10.1007/s11033-016-4054-3 · Cited by 96
“that some lncRNAs encompass regulatory functions, whereas others are exclusively products of transcription [24, 44].”
BackgroundInfluential
The long noncoding RNA‐ROR promotes the resistance of radiotherapy for human colorectal cancer cells by targeting the p53/miR‐145 pathway
Yang, P., Yang, Y., An, W., Xu, J., Zhang, G., Jie, J., & Zhang, Q. (2016) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.13606 · Cited by 97
Linc00659, a long noncoding RNA, acts as novel oncogene in regulating cancer cell growth in colorectal cancer
Tsai, K., Lo, Y.-H., Liu, H., Yeh, C.-Y., Chen, Y.-Z., Hsu, C.-W., Chen, W.-S., & Wang, J. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0821-1 · Cited by 97
“Using transcriptome data to determine which types of protein-coding genes are coexpressed with lncRNAs may facilitate exploring lncRNA function [37].”
Research progresses in roles of LncRNA and its relationships with breast cancer
Xu, B., Hongjian, Y., Zhang, X., Bo, C., Shifeng, Y., & Tang, B. (2018) · Cancer Cell International · doi:10.1186/s12935-018-0674-0 · Cited by 97
RNA Antisense Purification (RAP) for Mapping RNA Interactions with Chromatin
Engreitz, J., Lander, E. S., & Guttman, M. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-2253-6_11 · Cited by 103
Self-citation
Tyrosine phosphorylation of RNA polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells
Descostes, N., Heidemann, M., Spinelli, L., Schüller, R., Maqbool, M. A., Fenouil, R., Koch, F., Innocenti, C., Gut, M., Gut, I. G., et al. (2014) · eLife · doi:10.7554/elife.02105 · Cited by 99
A Novel RNA In Situ Hybridization Assay for the Long Noncoding RNA SChLAP1 Predicts Poor Clinical Outcome After Radical Prostatectomy in Clinically Localized Prostate Cancer
Mehra, R., Shi, Y., Udager, A. M., Prensner, J. R., Sahu, A., Iyer, M. K., Siddiqui, J., Cao, X., Wei, J., Jiang, H., et al. (2014) · Neoplasia · doi:10.1016/j.neo.2014.11.006 · Cited by 95
Epigenetic regulation of drug metabolism and transport
Peng, L., & Zhong, X. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.01.007 · Cited by 96
Regulatory long non-coding RNA and its functions
Huang, Y., Liu, N., Wang, J., Wang, Y. Q., Yu, X. L., Wang, Z. B., Cheng, X. C., & Zou, Q. (2012) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-012-0166-y · Cited by 95
Long non‐coding RNA NEAT1 is a transcriptional target of p53 and modulates p53‐induced transactivation and tumor‐suppressor function
Idogawa, M., Ohashi, T., Sasaki, Y., Nakase, H., & Tokino, T. (2017) · International Journal of Cancer · doi:10.1002/ijc.30689 · Cited by 98
Promising biomarkers of human aging: In search of a multi-omics panel to understand the aging process from a multidimensional perspective
Rivero-Segura, N. A., Bello‐Chavolla, O. Y., Barrera-Vázquez, O. S., Gutiérrez‐Robledo, L. M., & Gómez-Verján, J. C. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101164 · Cited by 99
Evolutionary conservation and functional roles of ncRNA
Qu, Z., & Adelson, D. L. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00205 · Cited by 100
Long Noncoding RNA: Its Physiological and Pathological Roles
Yan, B., & Wang, Z. (2012) · DNA and Cell Biology · doi:10.1089/dna.2011.1544 · Cited by 98
Long noncoding RNA MALAT1 as a potential therapeutic target in osteosarcoma
Cai, X., Liu, Y., Yang, W., Xia, Y. F., Cao, Y., Yang, S., & Liu, X. (2015) · Journal of Orthopaedic Research® · doi:10.1002/jor.23105 · Cited by 95
Plasma level of metastasis‐associated lung adenocarcinoma transcript 1 is associated with liver damage and predicts development of hepatocellular carcinoma
Konishi, H., Ichikawa, D., Yamamoto, Y., Arita, T., Shoda, K., Hiramoto, H., Hamada, J., Itoh, H., Fujita, Y., Komatsu, S., et al. (2015) · Cancer Science · doi:10.1111/cas.12854 · Cited by 95
Deconstructing the Dogma
Mattick, J. S. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04991.x · Cited by 97
Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations
Kadakkuzha, B. M., Liu, X.-A., McCrate, J., Shankar, G., Rizzo, V., Afinogenova, A., Young, B. M., Fallahi, M., Carvalloza, A. C., Raveendra, B., et al. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00063 · Cited by 96
Long non-coding RNA discovery across the genus anopheles reveals conserved secondary structures within and beyond the Gambiae complex
Jenkins, A. M., Waterhouse, R. M., & Muskavitch, M. A. T. (2015) · BMC Genomics · doi:10.1186/s12864-015-1507-3 · Cited by 95
Non‐coding RNAs and their epigenetic regulatory mechanisms
Zhou, H., Hu, H., & Lai, M. (2010) · Biology of the Cell · doi:10.1042/bc20100029 · Cited by 101
Distinct RNA degradation pathways and 3' extensions of yeast non-coding RNA species
Marquardt, S., Hazelbaker, D. Z., & Buratowski, S. (2011) · Transcription · doi:10.4161/trns.2.3.16298 · Cited by 94
Regulation of the ESC transcriptome by nuclear long noncoding RNAsPreprint
Bergmann, J. H., Li, J., Eckersley-Maslin, M. A., Rigo, F., Freier, S. M., & Spector, D. L. (2015) · Genome Research · doi:10.1101/gr.189027.114 · Cited by 93
Rôle des longs ARN non codants dans le développement normal et pathologique
Mathieu, È.-L., Belhocine, M., Dao, L. T. M., Puthier, D., & Spicuglia, S. (2014) · médecine/sciences · doi:10.1051/medsci/20143008018 · Cited by 101
LINC01354 interacting with hnRNP-D contributes to the proliferation and metastasis in colorectal cancer through activating Wnt/β-catenin signaling pathway
Li, J., He, M.-R., Xu, W., & Huang, S. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1150-y · Cited by 93
The Role of LncRNAs in Translation
Karakaş, D., & Özpolat, B. (2021) · Non-Coding RNA · doi:10.3390/ncrna7010016 · Cited by 102
Signaling by LncRNAs: Structure, Cellular Homeostasis, and Disease Pathology
Nadhan, R., Isidoro, C., Song, Y. S., & Dhanasekaran, D. N. (2022) · Cells · doi:10.3390/cells11162517 · Cited by 98
“In breast cancer, HOTAIR is overexpressed and interacts with PRC2 to induce the repressive histone methylation, which suppresses the expressions of several tumor-suppressor genes, thereby resulting in tumor invasion and metastasis [37,56,57].”
Background
Epigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs
Amin, V. R., Harris, R. A., Onuchic, V., Jackson, A. R., Charnecki, T., Paithankar, S., Subramanian, S. L., Riehle, K. P., Coarfa, C., & Milosavljevic, A. (2015) · Nature Communications · doi:10.1038/ncomms7370 · Cited by 93
Negative Correlation between Expression Level and Evolutionary Rate of Long Intergenic Noncoding RNAs
Managadze, D., Rogozin, I. B., Chernikova, D. A., Shabalina, S. A., & Koonin, E. V. (2011) · Genome Biology and Evolution · doi:10.1093/gbe/evr116 · Cited by 96
Databases for lncRNAs: a comparative evaluation of emerging tools
Fritah, S., Niclou, S. P., & Azuaje, F. J. (2014) · RNA · doi:10.1261/rna.044040.113 · Cited by 90
Chromatin Topology and the Regulation of Antigen Receptor Assembly
Bossen, C., Månsson, R., & Murre, C. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075003 · Cited by 98
Integrated Analysis of Dysregulated ncRNA and mRNA Expression Profiles in Humans Exposed to Carbon Nanotubes
Shvedova, A. A., Yanamala, N. V. K., Kisin, E. R., Оскарович, Х. Т., Birch, M. E., & Fatkhutdinova, L. M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150628 · Cited by 92
RETRACTED: LncRNA GAS5 suppresses the tumorigenesis of cervical cancer by downregulating miR-196a and miR-205
Yang, W., Li, H., Xu, X., Wang, Q., Huang, J., & Jiang, L. (2017) · Tumor Biology · doi:10.1177/1010428317711315 · Cited by 92
Retracted
LncRNA XIST acts as a tumor suppressor in prostate cancer through sponging miR-23a to modulate RKIP expression
Du, Y., Weng, X., Wang, L., Liu, X., Zhu, H., Guo, J., Ning, J., & Xiao, C. (2017) · Oncotarget · doi:10.18632/oncotarget.21719 · Cited by 92
Production of Spliced Long Noncoding RNAs Specifies Regions with Increased Enhancer Activity
Gil, N., & Ulitsky, I. (2018) · Cell Systems · doi:10.1016/j.cels.2018.10.009 · Cited by 88
Emerging impact of the long noncoding RNA MIR22HG on proliferation and apoptosis in multiple human cancers
Zhang, L., Li, C., & Su, X. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01784-8 · Cited by 90
“It is currently believed that > 90% of noncoding RNAs (ncRNAs) in the human genome play important biological roles, whereas they were previously considered “transcriptional noise” or “transcriptional waste” [1, 2].”
Background
miRNAs and lncRNAs as Novel Therapeutic Targets to Improve Cancer Immunotherapy
Martino, M. T. D., Riillo, C., Scionti, F., Grillone, K., Polerà, N., Caracciolo, D., Arbitrio, M., Tagliaferri, P., & Tassone, P. (2021) · Cancers · doi:10.3390/cancers13071587 · Cited by 98
“The lncRNA transcriptional process shares several features with mRNA transcription, including 5′-capping, 3′-polyadenylation, normal and alternative splicing mechanisms [24], RNA editing processes [25], and patterns of transcriptional activation [26].”
Background
From genotype to phenotype: genetics of mammalian long non-coding RNAs in vivo
Andergassen, D., & Rinn, J. L. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00427-8 · Cited by 98
Self-citation
Transcriptional gene silencing through epigenetic changes mediated by non-coding RNAs.
Malecová, B., & Morris, K. V. (2010) · PubMed · Cited by 92
microRNAs and ceRNAs: RNA networks in pathogenesis of cancer.
Su, X., Xing, J., Wang, Z., Chen, L., Cui, M., & Jiang, B. (2013) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.1000-9604.2013.03.08 · Cited by 93
Epigenetics: The Language of the Cell?
Huang, B., Jiang, C., & Zhang, R. (2014) · Epigenomics · doi:10.2217/epi.13.72 · Cited by 94
Epigenetics in cardiovascular disease
Shirodkar, A., & Marsden, P. A. (2011) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e328345986e · Cited by 92
Laying a solid foundation for Manhattan – ‘setting the functional basis for the post-GWAS era’
Zhang, X., Bailey, S. D., & Lupien, M. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.02.006 · Cited by 95
Mammalian microRNAs and long noncoding RNAs in the host-bacterial pathogen crosstalk
Duval, M., Cossart, P., & Lebreton, A. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.06.016 · Cited by 91
The lncRNA XIST exhibits oncogenic properties via regulation of miR-449a and Bcl-2 in human non-small cell lung cancer
Zhang, Y.-L., Li, X., Hou, Y.-X., Fang, N., You, J., & Zhou, Q. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2016.133 · Cited by 90
DNA damage repair alterations modulate M2 polarization of microglia to remodel the tumor microenvironment via the p53-mediated MDK expression in glioma
Meng, X., Duan, C., Pang, H., Chen, Q., Han, B. R., Zha, C., Dinislam, M., Wu, P., Li, Z., Zhao, S., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.01.067 · Cited by 93
“One hundred and forty genes involved in eight canonical DDR pathways [4,52] were used to calculate the DDR alterations for every sample of TCGA, Rembrandt and CGGA datasets by ssGSEA which estimates the degree of enrichment of DDR pathways in individual samples [12,53].”
Method
Expression and Functional Role of Reprogramming-Related Long Noncoding RNA (lincRNA-ROR) in Glioma
Feng, S., Yao, J., Chen, Y., Geng, P., Zhang, H., Ma, X., Zhao, J., & Yu, X. (2015) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0488-z · Cited by 91
The dark matter rises: the expanding world of regulatory RNAs
Clark, M. B., Choudhary, A., Smith, M. A., Taft, R. J., & Mattick, J. S. (2013) · Essays in Biochemistry · doi:10.1042/bse0540001 · Cited by 96
From “Cellular” RNA to “Smart” RNA: Multiple Roles of RNA in Genome Stability and Beyond
Michelini, F., Jalihal, A. P., Francia, S., Meers, C., Neeb, Z. T., Rossiello, F., Gioia, U., Aguado, J., Jones-Weinert, C., Luke, B., et al. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00487 · Cited by 85
Altered expression of long non-coding RNAs during genotoxic stress-induced cell death in human glioma cells
Liu, Q., Sun, S., Yu, W., Jiang, J., Zhuo, F., Qiu, G., Xu, S., & Jiang, X. (2015) · Journal of Neuro-Oncology · doi:10.1007/s11060-015-1718-0 · Cited by 90
Genome-Wide Identification of Long Intergenic Noncoding RNA Genes and Their Potential Association with Domestication in Pigs
Zhou, Z., Li, A., Adeola, A. C., Yan-hu, L., Irwin, D. M., Xie, H., & Zhang, Y. (2014) · Genome Biology and Evolution · doi:10.1093/gbe/evu113 · Cited by 91
The role of long non-coding RNAs in rheumatic diseases
Tang, Y., Zhou, T., Yu, X., Xue, Z., & Shen, N. (2017) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2017.162 · Cited by 90
Regulation of Neuroregeneration by Long Noncoding RNAs
Perry, R. B., Hezroni, H., Goldrich, M. J., & Ulitsky, I. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.09.021 · Cited by 95
“Advances in transcriptome mapping in the past decade revealed pervasive transcription outside of the boundaries of protein-coding genes (Guttman et al., 2009; Kapranov et al., 2007; Ravasi et al., 2006).”
Long Noncoding RNAs in Host–Pathogen Interactions
Agliano, F., Rathinam, V. A. K., Medvedev, A. E., Vanaja, S. K., & Vella, A. T. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.04.001 · Cited by 89

Authors: Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., Cabili, M. N., Jaenisch, R., Mikkelsen, T. S., Jacks, T., Hacohen, N., Bernstein, B. E., Kellis, M., Regev, A., Rinn, J. L., & Lander, E. S.
Affiliations: Broad Institute (US)
Koch Institute for Integrative Cancer Research At MIT (US)
Whitehead Institute for Biomedical Research (US)
Harvard University (US)
Corresponding author: Rinn, John L.
ORCID: Guttman, Mitchell
Amit, Ido
Garber, Manuel
French, Courtney
Lin, Michael F.
Feldser, David
Huarte, Maite
Zuk, Or
Cabili, Moran N.
Jaenisch, Rudolf
Mikkelsen, Tarjei S.
Jacks, Tyler
Hacohen, Nir
Bernstein, Bradley E.
Kellis, Manolis
Regev, Aviv
Rinn, John L.
Lander, Eric S.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2009-02-01
Volume: 458
Issue: 7235
Pages: 223-227
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature07672
PMC: PMC2754849
OpenAlex: W1999746344
Cited by: 4,098
References: 39
Citations by year: 2026: 34 · 2025: 85 · 2024: 128 · 2023: 168 · 2022: 233 · 2021: 331 · 2020: 274 · 2019: 301 · 2018: 331 · 2017: 330 · 2016: 322 · 2015: 334 · 2014: 315 · 2013: 266 · 2012: 249
FWCI: 72.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
Funders: National Institutes of Health (DP1OD003958)
National Human Genome Research Institute (U54HG003067, R01HG004037)
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 › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords: long intergenic non-coding RNA, chromatin state, evolutionary conservation, purifying selection, embryonic stem cell pluripotency, cell proliferation, transcription factor regulation, p53, NF-κB, SOX2, Oct4, Nanog, transcriptional noise
MeSH terms: Animals, Base Sequence, Cells, Cultured, Chromatin, Exons, Mammals, Promoter Regions, Genetic, RNA, Transcription Factors, Reproducibility of Results, Conserved Sequence, DNA, Intergenic, Mice

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

Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks