Roles for MicroRNAs in Conferring Robustness to Biological Processes
Open accessAbstract
Biological systems use a variety of mechanisms to maintain their functions in the face of environmental and genetic perturbations. Increasing evidence suggests that, among their roles as posttranscriptional repressors of gene expression, microRNAs (miRNAs) help to confer robustness to biological processes by reinforcing transcriptional programs and attenuating aberrant transcripts, and they may in some network contexts help suppress random fluctuations in transcript copy number. These activities have important consequences for normal development and physiology, disease, and evolution. Here, we will discuss examples and principles of miRNAs that contribute to robustness in animal systems.
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?
The vast majority of miRNA knock-out mice examined thus far lack any strong phenotypes under normal physiological conditions.
“Somewhat unexpectedly, the vast majority of miRNA knock-out mice examined thus far lack any strong phenotypes under normal physiological conditions (Ebert and Sharp, 2012;Mendell and Olson, 2012).”
From microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain (2015) · cites this paper as Ebert and Sharp, 2012
The “Absent and variable phenotypes” section says several mouse miRNA knockouts show no gross phenotype and gives miR-208 as an example with little phenotype under normal conditions. It does not establish that the vast majority of mouse knockouts examined lack strong phenotypes; its “most” statement concerns worms, not mice. No page number is available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe repertoire of miRNA targets is a key determinant of the biological role of a given miRNA.
“Thus, the repertoire of miRNA targets is a key determinant of the biological role of a given miRNA (Ebert and Sharp, 2012).”
From Scalable and deep profiling of mRNA targets for individual microRNAs with chimeric eCLIP (2022) · cites this paper as Ebert and Sharp, 2012
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
Most mammalian mRNAs are conserved targets of microRNAs
Friedman, R. C., Farh, K. K.-H., Burge, C. B., & Bartel, D. P. (2009) · Genome Research · doi:10.1101/gr.082701.108 · Cited by 8,462 · see citing works
The impact of microRNAs on protein output
Baek, D., Villén, J., Shin, C., Camargo, F. D., Gygi, S. P., & Bartel, D. P. (2008) · Nature · doi:10.1038/nature07242 · Cited by 3,592 · see citing works
Hsp90 as a capacitor for morphological evolution
Rutherford, S. L., & Lindquist, S. (1998) · Nature · doi:10.1038/24550 · Cited by 2,270 · see citing works
Stochastic mRNA Synthesis in Mammalian Cells
Raj, A., Peskin, C. S., Tranchina, D., Vargas, D. Y., & Tyagi, S. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040309 · Cited by 1,737 · see citing works
Mayr, C., & Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.06.016 · Cited by 1,613 · see citing works
The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution
Farh, K. K.-H., Grimson, A., Jan, C., Lewis, B. P., Johnston, W. K., Lim, L. P., Burge, C. B., & Bartel, D. P. (2005) · Science · doi:10.1126/science.1121158 · Cited by 1,484 · see citing works
Stark, A., Brennecke, J., Bushati, N., Russell, R. B., & Cohen, S. M. (2005) · Cell · doi:10.1016/j.cell.2005.11.023 · Cited by 1,080 · see citing works
Most Caenorhabditis elegans microRNAs Are Individually Not Essential for Development or Viability
Miska, E. A., Alvarez-Saavedra, E., Abbott, A. L., Lau, N. C., Hellman, A. B., McGonagle, S. M., Bartel, D. P., Ambros, V. R., & Horvitz, H. R. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030215 · Cited by 484 · cited 2× · see citing works
“In worms, most individual miRNA mutants show no gross phenotype (Miska et al., 2007); the same is true for several of the mouse knockouts generated to date, including miR-21, miR-210, miR-214, miR-206, and miR-143 (E. Olson, personal communication).”
Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA
Klein, M. E., Lioy, D. T., Ma, L., Impey, S., Mandel, G., & Goodman, R. H. (2007) · Nature Neuroscience · doi:10.1038/nn2010 · Cited by 444 · see citing works
Peterson, K. J., Dietrich, M. R., & McPeek, M. A. (2009) · BioEssays · doi:10.1002/bies.200900033 · Cited by 252 · see citing works
Intronic miR-26b controls neuronal differentiation by repressing its host transcript,<i>ctdsp2</i>
Dill, H., Linder, B., Fehr, A., & Fischer, U. (2012) · Genes & Development · doi:10.1101/gad.177774.111 · Cited by 125 · see citing works
Flagged first, then by citations
Research works printed but not linked: 74
- Abbott AL Alvarez-Saavedra E Miska EA Lau NC Bartel DP Horvitz HR Ambros V The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans Dev. Cell 2005 9 403 414 16139228 PMC3969732
- Acar M Mettetal JT van Oudenaarden A Stochastic switching as a survival strategy in fluctuating environments Nat. Genet 2008 40 471 475 18362885
- Arvey A Larsson E Sander C Leslie CS Marks DS Target mRNA abundance dilutes microRNA and siRNA activity Mol. Syst. Biol 2010 6 363 20404830 PMC2872614
- Bail S Swerdel M Liu H Jiao X Goff LA Hart RP Kiledjian M Differential regulation of microRNA stability RNA 2010 16 1032 1039 20348442 PMC2856875
- Bartel DP MicroRNAs: target recognition and regulatory functions Cell 2009 136 215 233 19167326 PMC3794896
- Blake WJ Balázsi G Kohanski MA Isaacs FJ Murphy KF Kuang Y Cantor CR Walt DR Collins JJ Phenotypic consequences of promoter-mediated transcriptional noise Mol. Cell 2006 24 853 865 17189188
- Bleris L Xie Z Glass D Adadey A Sontag E Benenson Y Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template Mol. Syst. Biol 2011 7 519 21811230 PMC3202791
- Bracken CP Gregory PA Kolesnikoff N Bert AG Wang J Shannon MF Goodall GJ A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition Cancer Res 2008 68 7846 7854 18829540
- Brenner JL Jasiewicz KL Fahley AF Kemp BJ Abbott AL Loss of individual microRNAs causes mutant phenotypes in sensitized genetic backgrounds in C. elegans Curr. Biol 2010 20 1321 1325 20579881 PMC2946380
- Burk U Schubert J Wellner U Schmalhofer O Vincan E Spaderna S Brabletz T A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells EMBO Rep 2008 9 582 589 18483486 PMC2396950
- Bushati N Stark A Brennecke J Cohen SM Temporal reciprocity of miRNAs and their targets during the maternal-to-zygotic transition in Drosophila Curr. Biol 2008 18 501 506 18394895
- Cağatay T Turcotte M Elowitz MB Garcia-Ojalvo J Süel GM Architecture-dependent noise discriminates functionally analogous differentiation circuits Cell 2009 139 512 522 19853288
- Cesana M Cacchiarelli D Legnini I Santini T Sthandier O Chinappi M Tramontano A Bozzoni I A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA Cell 2011 147 358 369 22000014 PMC3234495
- Calvo SE Pagliarini DJ Mootha VK Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans Proc. Natl. Acad. Sci. USA 2009 106 7507 7512 19372376 PMC2669787
- Choi PS Zakhary L Choi WY Caron S Alvarez-Saavedra E Miska EA McManus M Harfe B Giraldez AJ Horvitz HR Schier AF Dulac C Members of the miRNA-200 family regulate olfactory neurogenesis Neuron 2008 57 41 55 18184563 PMC2204047
- Choi WY Giraldez AJ Schier AF Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430 Science 2007 318 271 274 17761850
- Damiani D Alexander JJ O'Rourke JR McManus M Jadhav AP Cepko CL Hauswirth WW Harfe BD Strettoi E Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina J. Neurosci 2008 28 4878 4887 18463241 PMC3325486
- Dong Q Meng P Wang T Qin W Qin W Wang F Yuan J Chen Z Yang A Wang H MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2 PLoS One 2010 5 e10147 20418948 PMC2854685
- Ebert MS Neilson JR Sharp PA MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells Nat. Meth 2007 4 721 726 PMC3857099 17694064
- Fazi F Rosa A Fatica A Gelmetti V De Marchis ML Nervi C Bozzoni I A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis Cell 2005 123 819 831 16325577
- Garcia DM Baek D Shin C Bell GW Grimson A Bartel DP Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs Nat. Struct. Mol. Biol 2011 18 1139 1146 21909094 PMC3190056
- Gardner TS Cantor CR Collins JJ Construction of a genetic toggle switch in Escherichia coli Nature 2000 403 339 342 10659857
- Gerstein MB Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project Science 2010 330 1775 1787 21177976 PMC3142569
- Gibbons DL Lin W Creighton CJ Rizvi ZH Gregory PA Goodall GJ Thilaganathan N Du L Zhang Y Pertsemlidis A Kurie JM Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression Genes Dev 2009 23 2140 2151 19759262 PMC2751985
- Giraldez AJ Mishima Y Rihel J Grocock RJ Van Dongen S Inoue K Enright AJ Schier AF Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs Science 2006 312 75 79 16484454
- Guo H Ingolia NT Weissman JS Bartel DP Mammalian microRNAs predominantly act to decrease target mRNA levels Nature 2010 466 835-440 PMC2990499 20703300
- Heimberg AM Sempere LF Moy VN Donoghue PC Peterson KJ MicroRNAs and the advent of vertebrate morphological complexity Proc. Natl. Acad. Sci. USA 2008 105 2946 2950 18287013 PMC2268565
- Herranz H Cohen SM MicroRNAs and gene regulatory networks: managing the impact of noise in biological systems Genes Dev 2010 24 1339 1344 20595229 PMC2895193
- Hilgers V Bushati N Cohen SM Drosophila microRNAs 263a/b confer robustness during development by protecting nascent sense organs from apoptosis PLoS Biol 2010 8 e1000396 20563308 PMC2885982
- Hornstein E Shomron N Canalization of development by microRNAs Nat. Genet 2006 38 Suppl S20 S24 16736020
- Iliopoulos D Hirsch HA Struhl K An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation Cell 2009 139 693 706 19878981 PMC2783826
- Ji Z Lee JY Pan Z Jiang B Tian B Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development Proc. Natl. Acad. Sci. USA 2009 106 7028 7033 19372383 PMC2669788
- Kitano H Biological robustness Nat. Rev. Genet 2004 5 826 837 15520792
- Kumar MS Erkeland SJ Pester RE Chen CY Ebert MS Sharp PA Jacks T Suppression of non-small cell lung tumor development by the let-7 microRNA family Proc. Natl. Acad. Sci. USA 2008 105 3903 3908 18308936 PMC2268826
- Kumar MS Lu J Mercer KL Golub TR Jacks T Impaired microRNA processing enhances cellular transformation and tumorigenesis Nat. Genet 2007 39 673 677 17401365
- Kumar MS Pester RE Chen CY Lane K Chin C Lu J Kirsch DG Golub TR Jacks T Dicer1 functions as a haploinsufficient tumor suppressor Genes Dev 2009 23 2700 2704 19903759 PMC2788328
- Lee CT Risom T Strauss WM Evolutionary conservation of microRNA regulatory circuits: an examination of microRNA gene complexity and conserved microRNA-target interactions through metazoan phylogeny DNA Cell Biol 2007 26 209 218 17465887
- Lestas I Vinnicombe G Paulsson J Fundamental limits on the suppression of molecular fluctuations 2010 467 174 178 PMC2996232 20829788
- Leung AKL Vyas S Rood JE Bhutkar A Sharp PA Chang P Poly(ADP-ribose) regulates stress responses and microRNA activity in the cytoplasm Mol. Cell 2011 42 489 499 21596313 PMC3898460
- Levine E Zhang Z Kuhlman T Hwa T PLoS Biol 2007 5 e229 17713988 PMC1994261
- Li QJ Chau J Ebert PJ Sylvester G Min H Liu G Braich R Manoharan M Soutschek J Skare P Klein LO Davis MM Chen CZ miR-181a is an intrinsic modulator of T cell sensitivity and selection Cell 2007 129 147 161 17382377
- Li X Carthew RW A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye Cell 2005 123 1267 1277 16377567
- Li X Cassidy JJ Reinke CA Fischboeck S Carthew RW A microRNA imparts robustness against environmental fluctuation during development Cell 2009 137 273 282 19379693 PMC2674871
- Li Y Wang F Lee JA Gao FB MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila Genes Dev 2006 20 2793 2805 17015424 PMC1619947
- Linsley PS Schelter J Burchard J Kibukawa M Martin MM Bartz SR Johnson JM Cummins JM Raymond CK Dai H Chau N Cleary M Jackson AL Carleton M Lim L Transcripts Targeted by the MicroRNA-16 family cooperatively regulate cell cycle progression Mol. Cell Biol 2007 27 2240 2252 17242205 PMC1820501
- Lu J Getz G Miska EA Alvarez-Saavedra E Lamb J Peck D Sweet-Cordero A Ebert BL Mak RH Ferrando AA Downing JR Jacks T Horvitz HR Golub TR MicroRNA expression profiles classify human cancers Nature 2005 435 834 838 15944708
- Martinez NJ Ow MC Barrasa MI Hammell M Sequerra R Doucette-Stamm L Roth FP Ambros VR Walhout AJ A C. elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity Genes Dev 2008 22 2535 2549 18794350 PMC2546694
- Mayr C Hemann MT Bartel DP Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation Science 2007 315 1576 1579 17322030 PMC2556962
- Medeiros LA Dennis LM Gill ME Houbaviy H Markoulaki S Fu D White AC Kirak O Sharp PA Page DC Jaenisch R Mir-290-295 deficiency in mice results in partially penetrant embryonic lethality and germ cell defects Proc. Natl. Acad. Sci. USA 2011 108 14163 14168 21844366 PMC3161528
- Mishima Y Abreu-Goodger C Staton AA Stahlhut C Shou C Cheng C Gerstein M Enright AJ Giraldez AJ Zebrafish miR-1 and miR-133 shape muscle gene expression and regulate sarcomeric actin organization Genes Dev 2009 23 619 632 19240126 PMC2658521
- modENCODE Consortium Identification of functional elements and regulatory circuits by Drosophila modENCODE Science 2010 330 1787 1797 21177974 PMC3192495
- Mukherji S Ebert MS Zheng GZ Tsang JS Sharp PA van Oudenaarden A MicroRNAs can generate thresholds in target gene expression Nat. Genet 2011 43 854 859 21857679 PMC3163764
- Neilson JR Zheng GX Burge CB Sharp PA Dynamic regulation of miRNA expression in ordered stages of cellular development Genes Dev 2007 21 578 589 17344418 PMC1820899
- Osella M Bosia C Corá D Caselle M The role of incoherent microRNA-mediated feedforward loops in noise buffering PLoS Comput. Biol 2011 7 e1001101 21423718 PMC3053320
- Ozbudak EM Thattai M Kurtser I Grossman AD van Oudenaarden A Regulation of noise in the expression of a single gene Nat. Genet 2002 31 69 73 11967532
- Paulsson J Summing up the noise in gene networks Nature 2004 427 415 418 14749823
- Pedraza JM van Oudenaarden A Noise propagation in gene networks Science 2005 307 1965 1969 15790857
- Poliseno L Salmena L Zhang J Carver B Haveman WJ Pandolfi PP A coding-independent function of gene and pseudogene mRNAs regulates tumour biology Nature 2010 465 1033 1038 20577206 PMC3206313
- Papadopoulou AS Dooley J Linterman MA Pierson W Ucar O Kyewski B Zuklys S Hollander GA Matthys P Gray DH De Strooper B Liston A The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor Nat. Immunol 2011 13 181 187 22179202 PMC3647613
- Pulikkan JA Dengler V Peramangalam PS Peer Zada AA Müller-Tidow C Bohlander SK Tenen DG Behre G Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia Blood 2010 115 1768 1778 20029046 PMC2832809
- Raj A Rifkin SA Andersen E van Oudenaarden A Variability in gene expression underlies incomplete penetrance Nature 2010 463 913 918 20164922 PMC2836165
- Raser JM O'Shea EK Noise in gene expression: origins, consequences, and control Science 2005 309 2010 2013 16179466 PMC1360161
- Sandberg R Neilson JR Sarma A Sharp PA Burge CB Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites Science 2008 320 1643 1647 18566288 PMC2587246
- Seitz H Redefining microRNA targets Curr. Biol 2009 19 870 873 19375315
- Shkumatava A Stark A Sive H Bartel DP Coherent but overlapping expression of microRNAs and their targets during vertebrate development Genes Dev 2009 23 466 481 19240133 PMC2648652
- Smibert P Bejarano F Wang D Garaulet DL Yang JS Martin R Bortolamiol-Becet D Robine N Hiesinger PR Lai EC A Drosophila genetic screen yields allelic series of core microRNA biogenesis factors and reveals post-developmental roles for microRNAs RNA 2011 17 1997 2010 21947201 PMC3198593
- Sood P Krek A Zavolan M Macino G Rajewsky N Cell-type-specific signatures of microRNAs on target mRNA expression Proc. Natl. Acad. Sci. USA 2006 103 2746 2751 16477010 PMC1413820
- Staton AA Knaut H Giraldez AJ miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration Nat. Genet 2011 43 204 211 21258340 PMC3071589
- Sumazin P Yang X Chiu HS Chung WJ Iyer A Llobet-Navas D Rajbhandari P Bansal M Guarnieri P Silva J Califano A An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma Cell 2011 147 370 381 22000015 PMC3214599
- Tsang JS Ebert MS van Oudenaarden A Genome-wide dissection of microRNA functions and cotargeting networks using gene set signatures Mol. Cell 2010 38 140 153 20385095 PMC3110938
- Tsang J Zhu J van Oudenaarden A MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals Mol. Cell 2007 26 753 767 17560377 PMC2072999
- van Rooij E Sutherland LB Qi X Richardson JA Hill J Olson EN Control of stress-dependent cardiac growth and gene expression by a microRNA Science 2007 316 575 579 17379774
- Yoo AS Greenwald I LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans Science 2005 310 1330 1333 16239437 PMC3010395
- Zheng GX Ravi A Calabrese JM Medeiros LA Kirak O Dennis LM Jaenisch R Burge CB Sharp PA A latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells PLoS Genet 2011 7 e1002054 21573140 PMC3088722
Cited by
Sorted by citations
U1 snRNP regulates cancer cell migration and invasion in vitro
Oh, J.-M., Venters, C. C., Di, C., Pinto, A. M., Wan, L., Younis, I., Cai, Z., Arai, C., So, B. R., Duan, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13993-7 · Cited by 7,157 · see citing works
Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation
O'Brien, J., Hayder, H., Zayed, Y., & Peng, C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00402 · Cited by 5,287 · 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
Transcriptome and genome sequencing uncovers functional variation in humans
The Geuvadis Consortium, Lappalainen, T., Sammeth, M., Friedländer, M. R., ‘t Hoen, P. A. C., Monlong, J., Rivas, M. A., Gonzàlez-Porta, M., Kurbatova, N., Griebel, T., et al. (2013) · Nature · doi:10.1038/nature12531 · Cited by 1,888 · see citing works
MicroRNAs in cancer: biomarkers, functions and therapy
Hayes, J., Peruzzi, P. P., & Lawler, S. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.06.005 · Cited by 2,049 · see citing works
IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis
Rokavec, M., Öner, M. G., Li, H., Jackstadt, R., Jiang, L., Lodygin, D., Kaller, M., Horst, D., Ziegler, P. K., Schwitalla, S., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci73531 · Cited by 753 · see citing works
MicroRNAs as regulatory elements in immune system logic
Mehta, A., & Baltimore, D. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.40 · Cited by 704 · see citing works
MicroRNAs in the p53 network: micromanagement of tumour suppression
Hermeking, H. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3318 · Cited by 518 · see citing works
López-Otín, C., & Kroemer, G. (2021) · Cell · doi:10.1016/j.cell.2020.11.034 · Cited by 499 · see citing works
HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells
Tabet, F., Vickers, K. C., Cuesta Torres, L. F., Wiese, C. B., Shoucri, B. M., Lambert, G., Catherinet, C., Prado-Lourenco, L., Levin, M. G., Thacker, S., et al. (2014) · Nature Communications · doi:10.1038/ncomms4292 · Cited by 428 · see citing works
MicroRNA control of protein expression noise
Schmiedel, J. M., Klemm, S. L., Zheng, Y., Sahay, A., Blüthgen, N., Marks, D. S., & van Oudenaarden, A. (2015) · Science · doi:10.1126/science.aaa1738 · Cited by 395 · see citing works
The Mediator complex and transcription regulation
Poss, Z. C., Ebmeier, C. C., & Taatjes, D. J. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.840259 · Cited by 364 · see citing works
Deconstructing transcriptional heterogeneity in pluripotent stem cells
Kumar, R. M., Cahan, P., Shalek, A. K., Satija, R., Jay DaleyKeyser, A., Li, H., Zhang, J., Pardee, K., Gennert, D., Trombetta, J. J., et al. (2014) · Nature · doi:10.1038/nature13920 · Cited by 356 · see citing works
MicroRNAs shape the neuronal landscape
McNeill, E., & Van Vactor, D. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.005 · Cited by 274 · see citing works
Philipot, D., Guérit, D., Platano, D., Chuchana, P., Olivotto, E., Espinoza, F., Dorandeu, A., Pers, Y.-M., Piette, J., Borzi, R. M., et al. (2014) · Arthritis Research & Therapy · doi:10.1186/ar4494 · Cited by 226 · see citing works
MicroRNAs and neurodegeneration: role and impact
Abe, M., & Bonini, N. M. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.08.013 · Cited by 190 · see citing works
Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis
Jia, S.-Z., Yang, Y., Lang, J., Sun, P., & Leng, J. (2013) · Human Reproduction · doi:10.1093/humrep/des413 · Cited by 172 · see citing works
MiRNAs confer phenotypic robustness to gene networks by suppressing biological noise
Siciliano, V., Garzilli, I., Fracassi, C., Criscuolo, S., Ventre, S., & di Bernardo, D. (2013) · Nature Communications · doi:10.1038/ncomms3364 · Cited by 166 · see citing works
The Utility of Paradoxical Components in Biological Circuits
Hart, Y., & Alon, U. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.004 · Cited by 151 · see citing works
microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain
Kim, J., Yoon, H., Horie, T., Burchett, J. M., Restivo, J. L., Rotllan, N., Ramírez, C. M., Verghese, P. B., Ihara, M., Hoe, H.-S., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2053-15.2015 · Cited by 128 · see citing works
“In many cases, miRNA knock-out mice showed no gross phenotype under normal physiological conditions, possibly due to the functional redundancy of multiple miRNAs for the same target gene (Ebert and Sharp, 2012; Mendell and Olson, 2012).”
BackgroundA KRAB/KAP1-miRNA Cascade Regulates Erythropoiesis Through Stage-Specific Control of Mitophagy
Barde, I., Rauwel, B., Marin-Florez, R. M., Corsinotti, A., Laurenti, E., Verp, S., Offner, S., Marquis, J., Kapopoulou, A., Vanicek, J., et al. (2013) · Science · doi:10.1126/science.1232398 · Cited by 111 · see citing works
Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer’s disease.
Qian, Q., Zhang, J., He, F.-P., Bao, W.-X., Zheng, T.-T., Zhou, D.-M., Pan, H.-Y., Zhang, H., Zhang, X.-Q., He, X., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201801846r · Cited by 70 · see citing works
miR-1298 Inhibits Mutant KRAS-Driven Tumor Growth by Repressing FAK and LAMB3
Zhou, Y., Dang, J., Chang, K.-Y., Yau, E., Aza-Blanc, P., Moscat, J., & Rana, T. M. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2936 · Cited by 54 · see citing works
Barrier Function of the Repaired Skin Is Disrupted Following Arrest of Dicer in Keratinocytes
Ghatak, S., Chan, Y. C., Khanna, S., Banerjee, J., Weist, J., Roy, S., & Sen, C. K. (2015) · Molecular Therapy · doi:10.1038/mt.2015.65 · Cited by 54 · see citing works
Moszyńska, A., Jaśkiewicz, M., Serocki, M., Cabaj, A., Crossman, D. K., Bartoszewska, S., Gebert, M., Dąbrowski, M., Collawn, J. F., & Bartoszewski, R. (2022) · The FASEB Journal · doi:10.1096/fj.202101987r · Cited by 53 · see citing works
Scalable and deep profiling of mRNA targets for individual microRNAs with chimeric eCLIP
Manakov, S. A., Shishkin, A. A., Yee, B. A., Shen, K. A., Cox, D. C., Park, S. S., Foster, H. M., Chapman, K. B., Yeo, G. W., & Van Nostrand, E. L. (2022) · doi:10.1101/2022.02.13.480296 · Cited by 43 · see citing works
miRNAs in depression vulnerability and resilience: novel targets for preventive strategies
Lopizzo, N., Zonca, V., Cattane, N., Pariante, C. M., & Cattaneo, A. (2019) · Journal of Neural Transmission · doi:10.1007/s00702-019-02048-2 · Cited by 37 · see citing works
Pan, X.-Y., Wang, L., You, H.-M., Cheng, M., Yang, Y., Huang, C., & Li, J. (2021) · Laboratory Investigation · doi:10.1038/s41374-021-00531-7 · Cited by 26 · see citing works
MicroRNAs change the games in central nervous system pharmacology
Marangon, D., Raffaele, S., Fumagalli, M., & Lecca, D. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.06.019 · Cited by 22 · see citing works
MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration
Winkler, I., Engler, J. B., Vieira, V., Bauer, S., Liu, Y.-H., Di Liberto, G., Grochowska, K. M., Wagner, I., Bier, J., Bal, L. C., et al. (2023) · Science Advances · doi:10.1126/sciadv.adi6855 · Cited by 22 · see citing works
Gérard, C., Gonze, D., Lemaigre, F., & Novák, B. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003455 · Cited by 20 · see citing works
The miR-23-27-24 clusters drive lipid-associated macrophage proliferation in obese adipose tissue
Sprenkle, N. T., Winn, N. C., Bunn, K. E., Zhao, Y., Park, D. J., Giese, B. G., Karijolich, J. J., Ansel, K. M., Serezani, C. H., Hasty, A. H., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112928 · Cited by 19 · see citing works
Araujo, H. N., Lima, T. I., Guimarães, D. S. P. S. F., Oliveira, A. G., Favero-Santos, B. C., Branco, R. C. S., da Silva Araújo, R. M., Dantas, A. F. B., Castro, A., Chacon-Mikahil, M. P. T., et al. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00233.2020 · Cited by 17 · see citing works
Penning, A., Snoeck, S., Ormaechea, O. R., Ayyildiz, D., Polzer, O., Buitrago-Arango, M., Capobianco, R., de Winter, F., Balusu, S., Verhaagen, J., et al. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-026-02228-8 · Cited by 6 · see citing works
Murphy, R., Villegas-Salmerón, J., Sanz-Rodriguez, A., Engel, T., Mooney, C., Henshall, D. C., & Jimenez-Mateos, E. M. (2025) · PLOS One · doi:10.1371/journal.pone.0326401 · Cited by 3 · see citing works
Ali, S. Y., Prasad, A., & Das, D. (2025) · Physical Review E · doi:10.1103/physreve.111.014405 · Cited by 2 · see citing works
- Authors
- Ebert, M. S., & Sharp, P. A.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Corresponding author
- Sharp, Phillip A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 149
- Issue
- 3
- Pages
- 515-524
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3351105
- OpenAlex
- W2171296186
- Cited by
- 1,564
- References
- 11
- Citations by year
- 2026: 51 · 2025: 52 · 2024: 57 · 2023: 77 · 2022: 93 · 2021: 113 · 2020: 130 · 2019: 120 · 2018: 149 · 2017: 143 · 2016: 115 · 2015: 152 · 2014: 122 · 2013: 151 · 2012: 37
- FWCI
- 11.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Elsevier eBooks
- Funders
- National Institutes of Health (P30-CA14051)
- National Cancer Institute
- U.S. Public Health Service (R01-CA133404)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- microRNA, biological robustness, post-transcriptional regulation, stochastic gene expression, transcriptional programs, developmental stability, disease, evolution
- MeSH terms
- Animals, Drosophila melanogaster, Biological Evolution, Gene Expression Regulation, Humans, MicroRNAs
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