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Most Caenorhabditis elegans microRNAs Are Individually Not Essential for Development or Viability
Open accessAbstract
MicroRNAs (miRNAs), a large class of short noncoding RNAs found in many plants and animals, often act to post-transcriptionally inhibit gene expression. We report the generation of deletion mutations in 87 miRNA genes in Caenorhabditis elegans, expanding the number of mutated miRNA genes to 95, or 83% of known C. elegans miRNAs. We find that the majority of miRNAs are not essential for the viability or development of C. elegans, and mutations in most miRNA genes do not result in grossly abnormal phenotypes. These observations are consistent with the hypothesis that there is significant functional redundancy among miRNAs or among gene pathways regulated by miRNAs. This study represents the first comprehensive genetic analysis of miRNA function in any organism and provides a unique, permanent resource for the systematic study of miRNAs.
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“which may help to explain the robustness of miRNA regulatory networks and their resilience to mutations of individual miRNAs in knockout experiments (Miska et al., 2007).”
From Scalable and deep profiling of mRNA targets for individual microRNAs with chimeric eCLIP (2022) · cites this paper as Miska et al., 2007
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Cites
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Items 201–300 of 454
MicroRNAs as genetic sculptors: Fishing for clues
Takacs, C. M., & Giráldez, A. J. (2010) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2010.02.003 · Cited by 33
Human microRNAs co-silence in well-separated groups and have different predicted essentialities
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“This might explain, at least in part, why despite that complete loss of miRNA biogenesis being embryonic lethal ( Kanellopoulou et al., 2005; Wienholds et al., 2003), knockout of most miRNAs in mice produces no overt morphological or behavioral phenotypes (Miska et al., 2007; Mukherji et al., 2011).”
BackgroundAn in silico analysis of microRNAs: Mining the miRNAome
Murray, B. S., Choe, S. E., Woods, M. W., RYAN, T. E., & Liu, W. (2010) · Molecular BioSystems · doi:10.1039/c003961f · Cited by 40
Two MicroRNAs Are Sufficient for Embryonic Patterning in C. elegans
Dexheimer, P. J., Wang, J., & Cochella, L. (2020) · Current Biology · doi:10.1016/j.cub.2020.09.066 · Cited by 30
“elegans, most miRNAs are not required for viability in the lab, even at later stages [25].”
Cotargeting among microRNAs in the brain
Cherone, J. M., Jorgji, V., & Burge, C. B. (2019) · Genome Research · doi:10.1101/gr.249201.119 · Cited by 40
“However, genetic studies have found that individual miRNAs are often not essential for viability or development (Miska et al. 2007), and their regulatory roles are often difficult to detect, requiring knockout of multiple family members (Alvarez-Saavedra and Horvitz 2010) and/or environmental…”
BackgroundTissue Expression Pattern of PMK-2 p38 MAPK Is Established by the miR-58 Family in C. elegans
Pagano, D. J., Kingston, E. R., & Kim, D. H. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004997 · Cited by 32
“Since the initial genetic identification of microRNAs in Caenorhabditis elegans [1,2], biochemical cloning methods and computational approaches have identified hundreds of microRNAs [3,4], though genetic analysis has defined functional roles for relatively few of these [5,6].”
BackgroundMethodResultDiversity and Expression of MicroRNAs in the Filarial Parasite, Brugia malayi
Poole, C., Gu, W.-F., Kumar, S., Jin, J.-M., Davis, P., Bauché, D., & Mcreynolds, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096498 · Cited by 34
“For example, 7 of the 8 miR-36 family members are clustered within 800 nt on chromosome II [51,52].”
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García‐Hidalgo, M. C., González, J., Benitez, I. D., Carmona, P., Santisteve, S., Perez‐Pons, M., Moncusí‐Moix, A., Gort‐Paniello, C., Rodríguez‐Jara, F., Molinero, M., et al. (2022) · Emerging Microbes & Infections · doi:10.1080/22221751.2022.2081615 · Cited by 33
“Supporting the significant functional redundancy among miRNAs [36], although the individual miRNAs that composed the”
BackgroundKato, M., Kashem, M. A., & Cheng, C. (2016) · Aging · doi:10.18632/aging.101029 · Cited by 31
“elegans, for example, animals lacking individual miRNAs or even all members of a miRNA family do not display grossly abnormal phenotypes under standard laboratory conditions [24, 25].”
BackgroundMcEwen, T. J., Yao, Q., Yun, S., Lee, C.-Y., & Bennett, K. L. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.08.003 · Cited by 30
“Exceptions include deletions in two families, the miR51s or miR35s that each result in embryonic lethality (Miska et al., 2007; Alvarez-Saavedra and Horvitz, 2010).”
BackgroundResultInfluentialSmall RNA Regulators of T Cell-Mediated Autoimmunity
Jeker, L. T., & Bluestone, J. A. (2010) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9392-7 · Cited by 27
“elegans revealed that the majority of miRNAs was neither required for viability nor development [75].”
BackgroundImmunopurification of Ago1 miRNPs selects for a distinct class of microRNA targets
Hong, X., Hammell, M., Ambros, V., & Cohen, S. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908149106 · Cited by 44
Self-citationMarks, N. D., Winter, A. D., Gu, H. Y., Maitland, K., Gillan, V., Ambrož, M., Martinelli, A., Laing, R., MacLellan, R., Towne, J., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-54154-6 · Cited by 38
Systematic evaluation of C. elegans lincRNAs with CRISPR knockout mutants
Wei, S., Chen, H., Dzakah, E. E., Yu, B., Wang, X., Fu, T., Li, J., Liu, L., Fang, S., Liu, W., et al. (2019) · Genome biology · doi:10.1186/s13059-018-1619-6 · Cited by 41
Hao, P., & Waxman, D. J. (2018) · Endocrinology · doi:10.1210/en.2017-03109 · Cited by 31
Sun, K., Jee, D. I. H., de Navas, L. F., Duan, H., & Lai, E. C. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005245 · Cited by 31
“elegansmiRNAs, which revealed barely any developmental or behavioral phenotypes [12].”
BackgroundVilmos, P., Bujna, Á., Szuperak, M., Havelda, Z., Várallyay, É., Szabad, J., Kučerová, L., Somogyi, K., Kristó, I., Lukácsovich, T., et al. (2013) · Genetics · doi:10.1534/genetics.113.153585 · Cited by 31
“…the well-defined 59 end of mir-282 and the class I insulator-defined regulatory boundary predicted upstream from mir-282 by the modENCODE database (Négre et al. 2010), as well as a recent report on mir-282 being the target of the Drosha-Pasha complex (instead of the splicing machinery) (Kadener…”
BackgroundDallaire, A., Garand, C., Paquet, E., Mitchell, S., de Cabo, R., Simard, M. J., & Lebel, M. (2012) · Aging · doi:10.18632/aging.100489 · Cited by 31
“we measured the life span of worms carrying a deletion of the mir-124 gene (mir-124(n4255)) [33].”
MethodThe mir-51 Family of microRNAs Functions in Diverse Regulatory Pathways in Caenorhabditis elegans
Brenner, J. L., Kemp, B., & Abbott, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037185 · Cited by 31
Self-citationTranscription Factors Are Targeted by Differentially Expressed miRNAs in Primates
Dannemann, M., Prüfer, K., Lizano, E., Nickel, B., Burbano, H. A., & Kelso, J. F. (2012) · Genome Biology and Evolution · doi:10.1093/gbe/evs033 · Cited by 30
Biogenesis and Physiology of MicroRNAs
Melo, C. A., & Melo, S. A. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8444-8_2 · Cited by 32
“Therefore it is expected that a certain degree of redundancy will exist among miRNAs [ 7 , 8 ].”
BackgroundEpigenetics and Methylmercury-Induced Neurotoxicity, Evidence from Experimental Studies
Ke, T., Tinkov, A. A., Skalny, A. V., Santamarı́a, A., da Rocha, J. B. T., Bowman, A. B., Chen, W. L., & Aschner, M. (2023) · Toxics · doi:10.3390/toxics11010072 · Cited by 37
“elegans individual miRNA is not essential for development or viability [57]; however, they have important regulatory roles in embryonic morphogenesis [58], developmental timing [59], and numerous physiologic processes including locomotion, egg laying, and dauer entry [60].”
BackgroundGlobal identification of functional microRNA-mRNA interactions in Drosophila
Wessels, H., Lebedeva, S., Hirsekorn, A., Wurmus, R., Akalin, A., Mukherjee, N., & Ohler, U. (2019) · Nature Communications · doi:10.1038/s41467-019-09586-z · Cited by 53
RNA interference may result in unexpected phenotypes in Caenorhabditis elegans
De‐Souza, E. A., Camara, H., Salgueiro, W. G., Moro, R. D. P., Knittel, T. L., Tonon-da-Silva, G., Pinto, S., Pinca, A. P. F., Antebi, A., Pasquinelli, A. E., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz154 · Cited by 28
“mir-35-41 mutants exhibit reduced progeny viability when grown at restrictive temperature (25◦C), and this has been linked to embryonic and larval lethality (15,16,43,44).”
BackgroundThe Efficacy of Cardiac Anti-miR-208a Therapy Is Stress Dependent
Eding, J., Demkes, C. J., Lynch, J. M., Seto, A. G., Montgomery, R. L., Semus, H. M., Jackson, A. L., Isabelle, M., Chimenti, S., & van Rooij, E. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.01.012 · Cited by 29
“8,9 Instead, the actions of miRNAs in general seem to become pronounced under conditions of injury or stress.”
A tale of two sequences: microRNA-target chimeric reads
Broughton, J. P., & Pasquinelli, A. E. (2016) · Genetics Selection Evolution · doi:10.1186/s12711-016-0209-x · Cited by 27
“In C. elegans , the majority of single miRNA knockouts do not have an observable phenotype [15], as a consequence, the use of RNAi screens to detect targets that are regulated by miRNAs can be misleading.”
BackgroundJacobs, L., Bewicke-Copley, F., Poolman, M., Pink, R., Mulcahy, L. A., Baker, I. R., Beaman, E., Brooks, T., Caley, D., Cowling, W., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080844 · Cited by 30
“elegans [17], deletion of various miRNAs has no apparent consequence [18,19].”
BackgroundmiRNAs: small changes, widespread effects
Linsen, S. E. V., Tops, B. B. J., & Cuppen, E. P. J. G. (2008) · Cell Research · doi:10.1038/cr.2008.311 · Cited by 28
miR‐124 controls Drosophila behavior and is required for neural development
Wang, C., Feng, T., Wan, Q., Kong, Y., & Yuan, L.-D. (2014) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2014.08.006 · Cited by 26
“Surprisingly, knocking out mir-124 does not cause serious consequences in development (Miska et al., 2007), making this gene a quite complicated research focus.”
BackgroundResultWang, Y., Zhang, C., Fang, X., Zhao, Y., Chen, X., Sun, J., Zhou, Y., Wang, J., Wang, Y., Lan, X., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096857 · Cited by 32
“The family analysis of the identified miRNAs in our study showed that most members of conserved miRNAs families were expressed in caprine skeletal muscle, supporting the idea that regulatory or functional diversification has occurred [60– 61].”
Cell autonomous specification of temporal identity by Caenorhabditis elegans microRNA lin-4
Zhang, H., & Fire, A. Z. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.05.018 · Cited by 26
“In fact, the majority of microRNAs still have unknown functions; in particular, overt phenotypes have been missing in knockouts of a large subset of C. elegans microRNAs (Alvarez-Saavedra and Horvitz, 2010; Miska et al., 2007).”
BackgroundGenome-Wide Exploration of miRNA Function in Mammalian Muscle Cell Differentiation
Polesskaya, A., Degerny, C., Pinna, G., Maury, Y., Kratassiouk, G., Mouly, V., Morozova, N., Kropp, J., Frandsen, N., & Harel‐Bellan, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071927 · Cited by 28
“elegans [20] (in which, however, only 10% of the genome miRNAs were analyzed).”
BackgroundCooperative control of tumor suppressor genes by a network of oncogenic microRNAs
Mavrakis, K. J., Leslie, C. S., & Wendel, H. (2011) · Cell Cycle · doi:10.4161/cc.10.17.16959 · Cited by 34
Zhang, H., Artiles, K. L., & Fire, A. (2015) · RNA: A publication of the RNA Society · doi:10.1261/rna.053793.115 · Cited by 27
“Comprehensive studies on microRNA mutants have revealed that the absence of a single microRNA rarely results in a severe developmental phenotype, hampering efforts to uncover microRNA functions (Miska et al. 2007; Alvarez-Saavedra and Horvitz 2010).”
Methods for the discovery of new anti-aging products – targeted approaches
Manayi, A., Saeidnia, S., Gohari, A. R., & Abdollahi, M. R. (2014) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2014.885014 · Cited by 32
“Since mutants of miRNAs appear normal, decreasing miRNAs impacts the life span, which may be caused mainly by an adulthood deficiency compared to a developmental abnormality [27].”
BackgroundRole of microRNAs in Semaphorin function and neural circuit formation
Baudet, M., Bellon, A., & Holt, C. E. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.11.004 · Cited by 26
The role of miR-124a in early development of the Xenopus eye
Qiu, R., Liu, K., Liu, Y. M., Mo, W., Flynt, A. S., Patton, J. G., Kar, A. N., Wu, J. Y., & He, R. (2009) · Mechanisms of Development · doi:10.1016/j.mod.2009.08.002 · Cited by 26
“It has been reported that less than 10% of individual miRNA knockouts result in clear developmental or morphological defects in Caenorhabditis elegans (Miska et al., 2007), and most miRNAs might act redundantly with other miRNAs as fine-tuning regulators (Cao et al., 2007; Baroukh et al., 2007).”
BackgroundRecovery from heat shock requires the microRNA pathway in Caenorhabditis elegans
Pagliuso, D. C., Bodas, D. M., & Pasquinelli, A. E. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009734 · Cited by 27
“Consistent with the lack of obvious developmental defects in the miR-85 deletion mutants [38], few genes were up- (61 genes) or down-regulated (76 PLOS GENETICS Role of the MiRNA pathway in heat shock recovery”
Global identification of functional microRNA::mRNA interactions in Drosophila
Wessels, H., Lebedeva, S., Hirsekorn, A., Mukherjee, N., & Ohler, U. (2018) · bioRxiv · doi:10.1101/395335 · Cited by 26
Rebijith, K. B., Asokan, R., Ranjitha, H. H., & Kumar, N. K. K. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163635 · Cited by 25
Degradome sequencing reveals an endogenous microRNA target in C. elegans
Park, J. H., Ahn, S., Kim, S., Lee, J.-H., Nam, J.-W., & Shin, C. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.02.029 · Cited by 25
“phenotype in mir-249 mutants [26] or in ZK637.”
Exploiting Drosophila Genetics to Understand MicroRNA Function and Regulation
Dai, Q., Smibert, P., & Lai, E. C. (2012) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-387038-4.00008-2 · Cited by 21
Single‐cell mRNA profiling reveals the hierarchical response of miRNA targets to miRNA induction
Rzepiela, A. J., Viña‐Vilaseca, A., Breda, J., Ghosh, S., Syed, A. P., Gruber, A. J., Grandy, W. A., Eschbach, K., Beisel, C., Nimwegen, E. V., et al. (2018) · Molecular Systems Biology · doi:10.15252/msb.20188266 · Cited by 24
“…the founders of the class, the lin-4 and let-7 miRNA of Caenorhabditis elegans have striking developmental phenotypes (Ha et al, 1996; Wightman et al, 1993; Reinhart et al, 2000), most miRNA genes are individually dispensable for development and viability, at least in the worm (Miska et al, 2007).”
BackgroundDefinition and identification of small RNA sponges: Focus on miRNA sequestration
Migault, M., Donnou‐Fournet, E., Galibert, M., & Gilot, D. (2016) · Methods · doi:10.1016/j.ymeth.2016.11.012 · Cited by 28
Yang, S., Zhang, H., Guo, L., Zhao, Y., & Chen, F. (2014) · Gene · doi:10.1016/j.gene.2014.06.010 · Cited by 23
RNA Interference Links Oxidative Stress to the Inhibition of Heat Stress Adaptation
Spiró, Z., Arslan, M. A., Somogyvári, M., Nguyễn, M. T., Smolders, A., Dancsó, B., Németh, N., Elek, Z., Braeckman, B. P., Csermely, P., et al. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4161 · Cited by 18
“Single miRNAs do not seem to play an essential role in C. elegans development and growth, but both RNA interference and single miRNAs are indispensable to ensure proper development during environmental stress (20, 24, 31).”
The microRNAs of Caenorhabditis elegans
Kaufman, E., & Miska, E. A. (2010) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2010.07.001 · Cited by 119
Self-citationMicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease
Yoon, H., Flores, L. F., & Kim, J. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.04.020 · Cited by 23
“Moreover, it has been reported that many apparently unrelated miRNAs may have a common target gene, or sometimes one miRNA may target multiple genes in one pathway [95, 96].”
Backgroundcel-mir-237 and its homologue, hsa-miR-125b, modulate the cellular response to ionizing radiation
Metheetrairut, C., Adams, B. D., Nallur, S. V., Weidhaas, J. B., & Slack, F. J. (2016) · Oncogene · doi:10.1038/onc.2016.222 · Cited by 27
He, L., Xie, M., Huang, J., Zhang, T., Shi, S., & Tang, T. (2016) · Plant Cell Reports · doi:10.1007/s00299-016-1933-y · Cited by 23
“with previous observations in Caenorhabditis elegans that most miRNAs are indispensable for development or viability, but loss of an individual miRNA can cause mutant phenotypes in a sensitized genetic background (Miska et al. 2007; Brenner et al. 2010).”
ResultŠubašić, D., Brümmer, A., Wu, Y., Pinto, S. M., Imig, J., Keller, M., Jovanović, M., Lightfoot, H. L., Nasso, S., Götze, S., et al. (2015) · Genome Research · doi:10.1101/gr.183160.114 · Cited by 20
“elegans revealed strong phenotypes in several family mutants, while most single miRNA deletions had no effect on development or viability (Miska et al. 2007; Alvarez-Saavedra and Horvitz 2010; Shaw et al. 2010).”
An Intronic microRNA Links Rb/E2F and EGFR Signaling
Truscott, M., Islam, A. B. M. M. K., Lightfoot, J. W., López-Bigas, N., & Frolov, M. V. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004493 · Cited by 27
“loss-of-function phenotypes of a significant proportion of miRNAs has significantly hampered the characterization of their functions in vivo [1].”
BackgroundXiao, Y., Ping, Y., Fan, H., Xu, C. D., Guan, J., Zhao, H., Li, Y., Lv, Y., Jin, Y., Wang, L., et al. (2013) · Neuro-Oncology · doi:10.1093/neuonc/not018 · Cited by 23
MicroRNA-mediated gene regulation and the resilience of multicellular animals
Ambros, V. (2024) · Postępy Biochemii · doi:10.18388/pb.2021_515 · Cited by 26
“However, for many microRNAs, loss-of-function mu - tation of an individual microRNA gene results in no appar - ent phenotypes [40,41].”
BackgroundSelf-citationciRS-7 and miR-7 regulate ischemia induced neuronal death via glutamatergic signalingPreprint
Scoyni, F., Sitnikova, V., Giudice, L., Korhonen, P., Trevisan, D. M., de Sande, A. H., Gómez-Budia, M., Giniatullina, R., Ugidos, I. F., Dhungana, H., et al. (2024) · bioRxiv · doi:10.1101/2023.01.24.525136 · Cited by 22
“48,49 Moreover, unlike experimental settings involving acute treat-ment, KO models are subjected to the buffering effect of cellular adaptation.”
BackgroundHigh-Throughput Profiling of Caenorhabditis elegans Starvation-Responsive microRNAs
García-Segura, L., Abreu‐Goodger, C., Hernández-Mendoza, A., Dinkova, T. D., Padilla-Noriega, L., Pérez-Andrade, M. E., & Miranda‐Ríos, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142262 · Cited by 22
“Most embryo cells expressmir-35 members, first at the onset of gastrulation, with a peak at the onset of elongation [11,57,60].”
BackgroundAkay, A., Craig, A. L., Lehrbach, N., Larance, M., Pourkarimi, E., Wright, J. E., Lamond, A., Miska, E., & Gartner, A. (2013) · Open Biology · doi:10.1098/rsob.130151 · Cited by 22
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A miR Image of Stem Cells and Their Lineages
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Global, cell non-autonomous gene regulation drives individual lifespan among isogenic C. elegans
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“Systematic analysis of C. elegans miRNA knockouts yielded a similar perspective of few and/ or modest defects (Miska et al., 2007).”
Saul, N., Chakrabarti, S., Stürzenbaum, S. R., Menzel, R., & Steinberg, C. E. W. (2014) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2014.09.007 · Cited by 26
“let-7 is involved in the regulation of developmental timing and the reproduction process [59,62–64].”
MethodDeveloping microRNA screening as a functional genomics tool for disease research
Lemons, D., Maurya, M. R., Subramaniam, S., & Mercola, M. A. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00223 · Cited by 23
“On the other hand, deletion of certain miRNAs cause no discernible developmental phenotypes (Miska et al., 2007; Alvarez-Saavedra and Horvitz, 2010), indicating that they affect only a small number of targets which are relatively specialized or that their effect on their targets is only a small…”
BackgroundKemp, B. J., Allman, E. L., Immerman, L., Mohnen, M., Peters, M. A., Nehrke, K. W., & Abbott, A. L. (2012) · Current Biology · doi:10.1016/j.cub.2012.09.047 · Cited by 19
“The loss of mir-240/786 results in long and arrhythmic defecation cycles [22].”
Self-citationMicroRNAs: Genetically Sensitized Worms Reveal New Secrets
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Functional genomic analysis identifies miRNA repertoire regulating C. elegans oocyte development
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“Delineating miRNA function through knock-out and overexpression experiments in model organisms has had limited success, possibly because of functional redundancy among miRNAs or among gene pathways regulated by miRNAs [19].”
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“The following mutations and transgenes were used: LGIII: unc-119(ed3), LGIV: mir-58(n4640), LGX: alg-1(tm492), Transgene: opIs205(Peft-3::TAPtag::alg-1[genomics+39 UTR]; unc119[+]). unc-119(ed3) is described in Riddle et al. (1997) and mir58(n4640) in Miska et al. (2007).”
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“Of note, others have also shown that most microRNA deletions have a more subtle phenotype, or none at all (Miska et al. 2007).”
Micro-management of pluripotent stem cells
Guo, W., Wang, X., & Wang, Y. (2014) · Protein & Cell · doi:10.1007/s13238-013-0014-z · Cited by 21
“These global miRNA-knockout cells provide invaluable reagents to tackle the functions of miRNAs, as the functional characterization of miRNAs is often complicated by the redundancy of miRNA families (Miska et al., 2007).”
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“The deletion allele is from Miska et al. (2007).”
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“Worms lacking a single member of the mir-58 microRNA family do not display obvious defects (Miska et al., 2007), but those lacking four members of the mir-58 family, including mir-58, mir-80, mir-81, and mir-82, have a smaller body size and are defective in locomotion, pharyngeal pumping, dauer…”
BackgroundHSF-1 is a regulator of miRNA expression in Caenorhabditis elegans
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miR-58 family and TGF-β pathways regulate each other in Caenorhabditis elegans
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“This slow progress is caused, in part, by the fact that only a small minority of miRNAs shows an obvious phenotype when mutated (4).”
BackgroundFunctional microRNA screening using a comprehensive lentiviral human microRNA expression library
Poell, J. B., van Haastert, R. J., Cerisoli, F., Bolijn, A. S., Timmer, L. M., Diosdado, B., Meijer, G. A., van Puijenbroek, A. A. F. L., Berezikov, E., Schaapveld, R. Q. J., et al. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-546 · Cited by 19
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“Many miRNAs are members of paralogous families, which may redundantly regulate the same or related target mRNAs (Lau et al. 2001;Miska et al. 2007).”
BackgroundMicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis
LaPierre, M. P., Lawler, K., Godbersen, S., Farooqi, I. S., & Stoffel, M. (2022) · Nature Communications · doi:10.1038/s41467-022-33367-w · Cited by 18
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“[12], who reported that a deletion of mir-61, nDf59, does not cause overt vulval lineage defects.”
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CRISPR-Cas9 screens reveal common essential miRNAs in human cancer cell lines
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“Interestingly, early analyses in C. elegans have suggested a minor impact of miRNAs on cellular processes, as knockout experiments have revealed abnormal phenotypes for only a small fraction of miRNA mutants [5, 6].”
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“3A, igdb-2(ns122); daf-6(e1377) mutants expressing an igdb-2 cDNA::GFP fusion transgene under control of the glia-specific mir-228 promoter, expressed during channel morphogenesis (Miska et al., 2007), have significantly reduced dye accumulation compared to non-transgenic animals.”
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Metadata
- Authors
- 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.
- Affiliations
- Howard Hughes Medical Institute (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Horvitz, H. Robert
- ORCID
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-12-14
- Volume
- 3
- Issue
- 12
- Pages
- e215
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC2134938
- OpenAlex
- W2003952411
- Cited by
- 484
- References
- 111
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 17 · 2023: 14 · 2022: 12 · 2021: 15 · 2020: 16 · 2019: 21 · 2018: 24 · 2017: 28 · 2016: 29 · 2015: 33 · 2014: 46 · 2013: 39 · 2012: 60
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- e-Publications@Marquette (Marquette University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Ellison Medical Foundation
- Wellcome Trust (061641)
- National Institutes of Health (5f32gm065721-03)
- National Institute of General Medical Sciences (GM067031, R01GM067031, 5F32GM065721-02, GM34028, R01GM034028, F32 GM065721)
- 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 › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- microRNA, Caenorhabditis elegans, post-transcriptional regulation
- MeSH terms
- Animals, Mutation, Phenotype, Conserved Sequence, Caenorhabditis elegans, Genes, Helminth, Sequence Deletion, RNA, Helminth, Evolution, Molecular, MicroRNAs
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