Non-coding RNAs as regulators of embryogenesis (original) (raw)
Lee, R. C., Feinbaum, R. L. & Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell75, 843–854 (1993). CASPubMed Google Scholar
Wightman, B., Ha, I. & Ruvkun, G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell75, 855–862 (1993). CASPubMed Google Scholar
Brown, C. J. et al. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell71, 527–542 (1992). CASPubMed Google Scholar
Brockdorff, N. et al. The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell71, 515–526 (1992). CASPubMed Google Scholar
Borsani, G. et al. Characterization of a murine gene expressed from the inactive X chromosome. Nature351, 325–329 (1991). CASPubMed Google Scholar
Jacob, F. & Monod, J. Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol.3, 318–356 (1961). CASPubMed Google Scholar
Britten, R. J. & Davidson, E. H. Gene regulation for higher cells: a theory. Science165, 349–357 (1969). CASPubMed Google Scholar
Mattick, J. S., Taft, R. J. & Faulkner, G. J. A global view of genomic information-moving beyond the gene and the master regulator. Trends Genet.26, 21–28 (2009). PubMed Google Scholar
Jacquier, A. The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nature Rev. Genet.10, 833–844 (2009). CASPubMed Google Scholar
Carninci, P. Molecular biology: the long and short of RNAs. Nature457, 974–975 (2009). CASPubMed Google Scholar
Mercer, T., Dinger, M. & Mattick, J. Long non-coding RNAs: insights into functions. Nature Rev. Genet.10, 155–159 (2009). CASPubMed Google Scholar
Bushati, N. & Cohen, S. M. microRNA functions. Annu. Rev. Cell Dev. Biol.23, 175–205 (2007). CASPubMed Google Scholar
Koziol, M. J. & Rinn, J. L. RNA traffic control of chromatin complexes. Curr. Opin. Genet. Dev.20, 142–148 (2010). CASPubMedPubMed Central Google Scholar
Henderson, I. R. & Jacobsen, S. E. Epigenetic inheritance in plants. Nature447, 418–424 (2007). CASPubMed Google Scholar
Wollmann, H. & Weigel, D. Small RNAs in flower development. Eur. J. Cell Biol.89, 250–257 (2010). CASPubMed Google Scholar
Chitwood, D. H. & Timmermans, M. C. Small RNAs are on the move. Nature467, 415–419 (2010). CASPubMed Google Scholar
Swiezewski, S., Liu, F., Magusin, A. & Dean, C. Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target. Nature462, 799–802 (2009). CASPubMed Google Scholar
Okamura, K. & Lai, E. C. Endogenous small interfering RNAs in animals. Nature Rev. Mol. Cell Biol.9, 673–678 (2008). CAS Google Scholar
Ghildiyal, M. & Zamore, P. D. Small silencing RNAs: an expanding universe. Nature Rev. Genet.10, 94–108 (2009). CASPubMed Google Scholar
Giraldez, A. J. et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science308, 833–838 (2005). CASPubMed Google Scholar
Giraldez, A. J. et al. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science312, 75–79 (2006). This study demonstrates that a single miRNA family promotes the concerted elimination of hundreds of maternal RNAs in zebrafish and thereby sharpens the transition between maternal and zygotic gene expression programmes. The authors furthermore show that miR-430 destabilizes target mRNAs by causing their deadenylation. CASPubMed Google Scholar
Choi, W.-Y., Giraldez, A. J. & Schier, A. F. Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science318, 271–274 (2007). This study provides evidence for the physiological role of specific miRNA–mRNA interactions. Interference with miR-430 targeting of the Nodal agonist and antagonist by 'target protectors' identifies essential roles for miR-430 in regulating this key embryonic signalling pathway. CASPubMed Google Scholar
Wang, Y., Medvid, R., Melton, C., Jaenisch, R. & Blelloch, R. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nature Genet.39, 380–385 (2007). CASPubMed Google Scholar
Suh, N. et al. MicroRNA function is globally suppressed in mouse oocytes and early embryos. Curr. Biol.20, 271–277 (2010). CASPubMedPubMed Central Google Scholar
Alvarez-Saavedra, E. & Horvitz, H. R. Many families of C. elegans microRNAs are not essential for development or viability. Curr. Biol.20, 367–373 (2010). To date, this study provides the most comprehensive analyses of miRNA functionin vivo. Loss-of-function mutants for individual as well as all members of redundantly acting miRNA families often revealed no or only subtle phenotypes. These results highlight the importance and challenge of miRNA loss-of-function analyses. CASPubMedPubMed Central Google Scholar
Brenner, J. L., Jasiewicz, K. L., Fahley, A. F., Kemp, B. J. & Abbott, A. L. Loss of individual microRNAs causes mutant phenotypes in sensitized genetic backgrounds in C. elegans. Curr. Biol.20, 1321–1325 (2010). CASPubMedPubMed Central Google Scholar
Tadros, W. & Lipshitz, H. D. The maternal-to-zygotic transition: a play in two acts. Development136, 3033–3042 (2009). CASPubMed Google Scholar
Schier, A. F. The maternal-zygotic transition: death and birth of RNAs. Science316, 406–407 (2007). CASPubMed Google Scholar
Lund, E., Liu, M., Hartley, R. S., Sheets, M. D. & Dahlberg, J. E. Deadenylation of maternal mRNAs mediated by miR-427 in Xenopus laevis embryos. RNA15, 2351–2363 (2009). CASPubMedPubMed Central Google Scholar
Bushati, N., Stark, A., Brennecke, J. & Cohen, S. M. Temporal reciprocity of miRNAs and their targets during the maternal-to-zygotic transition in Drosophila. Curr. Biol.18, 501–506 (2008). CASPubMed Google Scholar
Wu, E. et al. Pervasive and cooperative deadenylation of 3′UTRs by embryonic MicroRNA families. Mol. Cell40, 558–570 (2010). CASPubMedPubMed Central Google Scholar
Rouget, C. et al. Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Nature467, 1128–1132 (2010). CASPubMedPubMed Central Google Scholar
Mishima, Y. et al. Differential regulation of germline mRNAs in soma and germ cells by zebrafish miR-430. Curr. Biol.16, 2135–2142 (2006). CASPubMedPubMed Central Google Scholar
Kedde, M. et al. RNA-binding protein Dnd1 inhibits microRNA access to target mRNA. Cell131, 1273–1286 (2007). This study describes one of the first examples for mechanisms that modulate miRNA activity. The conserved RNA-binding protein DND1 counteracts miRNA-mediated repression in human cells and zebrafish primordial germ cells. CASPubMed Google Scholar
Takeda, Y., Mishima, Y., Fujiwara, T., Sakamoto, H. & Inoue, K. DAZL relieves miRNA-mediated repression of germline mRNAs by controlling poly(A) tail length in zebrafish. PLoS ONE4, e7513 (2009). PubMedPubMed Central Google Scholar
Kee, K., Angeles, V. T., Flores, M., Nguyen, H. N. & Reijo Pera, R. A. Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Nature462, 222–225 (2009). CASPubMedPubMed Central Google Scholar
Landgraf, P. et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell129, 1401–1414 (2007). CASPubMedPubMed Central Google Scholar
Bernstein, E. et al. Dicer is essential for mouse development. Nature Genet.35, 215–217 (2003). CASPubMed Google Scholar
Murchison, E. P., Partridge, J. F., Tam, O. H., Cheloufi, S. & Hannon, G. J. Characterization of Dicer-deficient murine embryonic stem cells. Proc.Natl Acad. Sci. USA102, 12135–12140 (2005). CASPubMedPubMed Central Google Scholar
Kanellopoulou, C. et al. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev.19, 489–501 (2005). CASPubMedPubMed Central Google Scholar
Wang, Y. et al. Embryonic stem cell-specific microRNAs regulate the G1-S transition and promote rapid proliferation. Nature Genet.40, 1478–1483 (2008). This paper provides compelling evidence that miRNAs are essential for ES cell self-renewal. Expression of a single miRNA family member of the ESCC miRNAs can rescue the proliferation defect of ES cells that lack mature miRNAs. CASPubMed Google Scholar
Judson, R. L., Babiarz, J. E., Venere, M. & Blelloch, R. Embryonic stem cell-specific microRNAs promote induced pluripotency. Nature Biotech.27, 459–461 (2009). CAS Google Scholar
Melton, C., Judson, R. L. & Blelloch, R. Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature463, 621–626 (2010). This study presents evidence that two opposing families of miRNAs control ES cell maintenance and differentiation. Self-renewal-promoting ESCC miRNAs (see also reference 44) are antagonized by let-7, which functions as a regulator of ES cell differentiation. CASPubMedPubMed Central Google Scholar
Johnson, C. D. et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res.67, 7713–7722 (2007). CASPubMed Google Scholar
Rybak, A. et al. The let-7 target gene mouse lin-41 is a stem cell specific E3 ubiquitin ligase for the miRNA pathway protein Ago2. Nature Cell Biol.11, 1411–1420 (2009). CASPubMed Google Scholar
Wang, Y., Keys, D. N., Au-Young, J. K. & Chen, C. MicroRNAs in embryonic stem cells. J. Cell. Physiol.218, 251–255 (2009). CASPubMed Google Scholar
Marson, A. et al. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell134, 521–533 (2008). CASPubMedPubMed Central Google Scholar
Xu, N., Papagiannakopoulos, T., Pan, G., Thomson, J. & Kosik, K. MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell137, 647–658 (2009). CASPubMed Google Scholar
Newman, M. A., Thomson, J. M. & Hammond, S. M. Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA14, 1539–1549 (2008). CASPubMedPubMed Central Google Scholar
Viswanathan, S., Daley, G. & Gregory, R. Selective blockade of microRNA processing by Lin28. Science320, 97–100 (2008). References 52 and 53 identify the stem cell factor and RNA-binding protein LIN28 as an inhibitor of let-7 maturation. CASPubMedPubMed Central Google Scholar
Heo, I. et al. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. Mol. Cell32, 276–284 (2008). CASPubMed Google Scholar
Rybak, A. et al. A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nature Cell Biol.10, 987–993 (2008). CASPubMed Google Scholar
Krol, J., Loedige, I. & Filipowicz, W. The widespread regulation of microRNA biogenesis, function and decay. Nature Rev. Genet.11, 597–610 (2010). CASPubMed Google Scholar
Nakagawa, M. et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature Biotech.26, 101–106 (2008). CAS Google Scholar
West, J. A. et al. A role for Lin28 in primordial germ-cell development and germ-cell malignancy. Nature460, 909–913 (2009). CASPubMedPubMed Central Google Scholar
Guttman, M. et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature458, 223–227 (2009). In this first comprehensive study of lncRNAs, the authors use the chromatin signature of RNA polymerase II-transcribed regions (H3K4me3 and H3K36me3) to identify lincRNAs in four mouse cell types. Many of these lincRNAs are predicted to function in a wide range of biological processes. CASPubMedPubMed Central Google Scholar
Guttman, M. et al. Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs. Nature Biotech.28, 503–510 (2010). CAS Google Scholar
Sheik Mohamed, J., Gaughwin, P. M., Lim, B., Robson, P. & Lipovich, L. Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA16, 324–337 (2009). PubMed Google Scholar
Dinger, M. E. et al. Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res.18, 1433–1445 (2008). CASPubMedPubMed Central Google Scholar
Loewer, S. et al. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nature Genet.42, 1113–1117 (2010). CASPubMed Google Scholar
Martello, G. et al. MicroRNA control of Nodal signalling. Nature449, 183–188 (2007). CASPubMed Google Scholar
Rosa, A., Spagnoli, F. M. & Brivanlou, A. H. The miR-430/427/302 family controls mesendodermal fate specification via species-specific target selection. Dev. Cell16, 517–527 (2009). CASPubMed Google Scholar
Flynt, A. S., Li, N., Thatcher, E. J., Solnica-Krezel, L. & Patton, J. G. Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate. Nature Genet.39, 259–263 (2007). CASPubMed Google Scholar
Leucht, C. et al. MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary. Nature Neurosci.11, 641–648 (2008). CASPubMed Google Scholar
Li, Y., Wang, F., Lee, J.-A. & Gao, F.-B. MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila. Genes Dev.20, 2793–2805 (2006). CASPubMedPubMed Central Google Scholar
Lai, E. C., Tam, B. & Rubin, G. M. Pervasive regulation of Drosophila Notch target genes by GY-box-, Brd-box-, and K-box-class microRNAs. Genes Dev.19, 1067–1080 (2005). CASPubMedPubMed Central Google Scholar
Lee, J. T. Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome. Genes Dev.23, 1831–1842 (2009). CASPubMedPubMed Central Google Scholar
Koerner, M. V., Pauler, F. M., Huang, R. & Barlow, D. P. The function of non-coding RNAs in genomic imprinting. Development136, 1771–1783 (2009). CASPubMed Google Scholar
Schmidt, J. V., Levorse, J. M. & Tilghman, S. M. Enhancer competition between H19 and Igf2 does not mediate their imprinting. Proc. Natl Acad. Sci. USA96, 9733–9738 (1999). CASPubMedPubMed Central Google Scholar
Mancini-Dinardo, D., Steele, S. J., Levorse, J. M., Ingram, R. S. & Tilghman, S. M. Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev.20, 1268–1282 (2006). CASPubMedPubMed Central Google Scholar
Sleutels, F., Zwart, R. & Barlow, D. P. The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature415, 810–813 (2002). CASPubMed Google Scholar
Umlauf, D. et al. Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes. Nature Genet.36, 1296–1300 (2004). CASPubMed Google Scholar
Nagano, T. et al. The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science322, 1717–1720 (2008). CASPubMed Google Scholar
Pandey, R. R. et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol. Cell32, 232–246 (2008). References 77 and 78 demonstrate essential roles for imprinted lncRNAs in recruiting chromatin modifiers to neighbouring genes, resulting in monoallelic silencing of entire gene clusters incis. CASPubMed Google Scholar
Terranova, R. et al. Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. Dev. Cell15, 668–679 (2008). CASPubMed Google Scholar
Mohammad, F., Mondal, T., Guseva, N., Pandey, G. K. & Kanduri, C. Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development137, 2493–2499 (2010). CASPubMed Google Scholar
Haig, D. Genomic imprinting and kinship: how good is the evidence? Annu. Rev. Genet.38, 553–585 (2004). CASPubMed Google Scholar
Penny, G. D., Kay, G. F., Sheardown, S. A., Rastan, S. & Brockdorff, N. Requirement for Xist in X chromosome inactivation. Nature379, 131–137 (1996). CASPubMed Google Scholar
Ogawa, Y., Sun, B. K. & Lee, J. T. Intersection of the RNA interference and X-inactivation pathways. Science320, 1336–1341 (2008). CASPubMedPubMed Central Google Scholar
Kanellopoulou, C. et al. X chromosome inactivation in the absence of Dicer. Proc. Natl Acad. Sci. USA106, 1122–1127 (2009). CASPubMedPubMed Central Google Scholar
Sun, B. K., Deaton, A. M. & Lee, J. T. A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. Mol. Cell21, 617–628 (2006). CASPubMed Google Scholar
Tian, D., Sun, S. & Lee, J. T. The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell143, 390–403 (2010). CASPubMedPubMed Central Google Scholar
Wutz, A., Rasmussen, T. P. & Jaenisch, R. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nature Genet.30, 167–174 (2002). CASPubMed Google Scholar
Navarro, P., Page, D. R., Avner, P. & Rougeulle, C. Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program. Genes Dev.20, 2787–2792 (2006). CASPubMedPubMed Central Google Scholar
Zhao, J., Sun, B. K., Erwin, J. A., Song, J.-J. & Lee, J. T. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science322, 750–756 (2008). Analogous to the function of imprinted ncRNAs (see references 77 and 78), this study provides evidence that a conserved ncRNA originating from the Xic recruits repressive chromatin-modifying complexes of the Polycomb group family (PRC2) incis. Recruitment of PRC2 is essential for the nucleation of silencing of one entire X chromosome in mammalian females. CASPubMedPubMed Central Google Scholar
Gelbart, M. E. & Kuroda, M. I. Drosophila dosage compensation: a complex voyage to the X chromosome. Development136, 1399–1410 (2009). CASPubMedPubMed Central Google Scholar
Akhtar, A. & Becker, P. B. Activation of transcription through histone H4 acetylation by MOF, an acetyltransferase essential for dosage compensation in Drosophila. Mol. Cell5, 367–375 (2000). CASPubMed Google Scholar
Meller, V. H. & Rattner, B. P. The roX genes encode redundant male-specific lethal transcripts required for targeting of the MSL complex. EMBO J.21, 1084–1091 (2002). CASPubMedPubMed Central Google Scholar
Deng, X., Rattner, B. P., Souter, S. & Meller, V. H. The severity of roX1 mutations is predicted by MSL localization on the X chromosome. Mech. Dev.122, 1094–1105 (2005). CASPubMed Google Scholar
Stuckenholz, C., Meller, V. H. & Kuroda, M. I. Functional redundancy within roX1, a noncoding RNA involved in dosage compensation in Drosophila melanogaster. Genetics164, 1003–1014 (2003). CASPubMedPubMed Central Google Scholar
Gilfillan, G. D. et al. Chromosome-wide gene-specific targeting of the Drosophila dosage compensation complex. Genes Dev.20, 858–870 (2006). CASPubMedPubMed Central Google Scholar
Alekseyenko, A. A. et al. A sequence motif within chromatin entry sites directs MSL establishment on the Drosophila X chromosome. Cell134, 599–609 (2008). CASPubMedPubMed Central Google Scholar
Kind, J. & Akhtar, A. Cotranscriptional recruitment of the dosage compensation complex to X-linked target genes. Genes Dev.21, 2030–2040 (2007). CASPubMedPubMed Central Google Scholar
Lewis, E. B. A gene complex controlling segmentation in Drosophila. Nature276, 565–570 (1978). CASPubMed Google Scholar
Lipshitz, H. D., Peattie, D. A. & Hogness, D. S. Novel transcripts from the Ultrabithorax domain of the bithorax complex. Genes Dev.1, 307–322 (1987). CASPubMed Google Scholar
Bender, W. & Fitzgerald, D. Transcription activates repressed domains in the Drosophila bithorax complex. Development129, 4923–4930 (2002). CASPubMed Google Scholar
Hogga, I. & Karch, F. Transcription through the iab-7 _cis_-regulatory domain of the bithorax complex interferes with maintenance of Polycomb-mediated silencing. Development129, 4915–4922 (2002). CASPubMed Google Scholar
Petruk, S. et al. Transcription of bxd noncoding RNAs promoted by trithorax represses Ubx in cis by transcriptional interference. Cell127, 1209–1221 (2006). CASPubMedPubMed Central Google Scholar
Sanchez-Elsner, T., Gou, D., Kremmer, E. & Sauer, F. Noncoding RNAs of trithorax response elements recruit Drosophila Ash1 to Ultrabithorax. Science311, 1118–1123 (2006). CASPubMed Google Scholar
Martianov, I., Ramadass, A., Serra Barros, A., Chow, N. & Akoulitchev, A. Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature445, 666–670 (2007). CASPubMed Google Scholar
Kanhere, A. et al. Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. Mol. Cell38, 675–688 (2010). CASPubMedPubMed Central Google Scholar
Rinn, J. L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell129, 1311–1323 (2007). CASPubMedPubMed Central Google Scholar
Tsai, M.-C. et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science329, 689–693 (2010). References 107 and 108 identify the lncRNAHOTAIRastrans-acting repressor of gene expression of the HOXD cluster (reference 107) and of several other loci throughout the genome (reference 108).HOTAIR's silencing activity arises from its interaction with at least two repressive chromatin-modifying complexes, PRC2 (references 107,108) and LSD1–CoREST–REST (reference 108). CASPubMedPubMed Central Google Scholar
Gupta, R. A. et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature464, 1071–1076 (2010). CASPubMedPubMed Central Google Scholar
Zappulla, D. C. & Cech, T. R. RNA as a flexible scaffold for proteins: yeast telomerase and beyond. Cold Spring Harb. Symp. Quant. Biol.71, 217–224 (2006). CASPubMed Google Scholar
Khalil, A. M. et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc. Natl Acad. Sci. USA106, 11667–11672 (2009). CASPubMedPubMed Central Google Scholar
Huarte, M. et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell142, 409–419 (2010). CASPubMedPubMed Central Google Scholar
Bond, A. M. et al. Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry. Nature Neurosci.12, 1020–1027 (2009). One of the fewin vivostudies on lncRNA function available to date; phenotypic analysis ofEvf2lncRNA knockout mice provides evidence that this lncRNA has essential roles for the development and function of GABAergic neurons. CASPubMed Google Scholar
Yekta, S., Shih, I.-H. & Bartel, D. P. MicroRNA-directed cleavage of HOXB8 mRNA. Science304, 594–596 (2004). CASPubMed Google Scholar
Mansfield, J. H. et al. MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nature Genet.36, 1079–1083 (2004). CASPubMed Google Scholar
Stark, A. et al. A single Hox locus in Drosophila produces functional microRNAs from opposite DNA strands. Genes Dev.22, 8–13 (2008). CASPubMedPubMed Central Google Scholar
Ronshaugen, M., Biemar, F., Piel, J., Levine, M. & Lai, E. C. The Drosophila microRNA iab-4 causes a dominant homeotic transformation of halteres to wings. Genes Dev.19, 2947–2952 (2005). CASPubMedPubMed Central Google Scholar
Tyler, D. M. et al. Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci. Genes Dev.22, 26–36 (2008). CASPubMedPubMed Central Google Scholar
Thomsen, S., Azzam, G., Kaschula, R., Williams, L. S. & Alonso, C. R. Developmental RNA processing of 3′UTRs in Hox mRNAs as a context-dependent mechanism modulating visibility to microRNAs. Development137, 2951–2960 (2010). CASPubMed Google Scholar
Amaral, P. P. & Mattick, J. S. Noncoding RNA in development. Mamm. Genome19, 454–492 (2008). CASPubMed Google Scholar
Gao, F. B. Context-dependent functions of specific microRNAs in neuronal development. Neural Dev.5, 25 (2010). PubMedPubMed Central Google Scholar
Conaco, C., Otto, S., Han, J.-J. & Mandel, G. Reciprocal actions of REST and a microRNA promote neuronal identity. Proc. Natl Acad. Sci. USA103, 2422–2427 (2006). CASPubMedPubMed Central Google Scholar
Visvanathan, J., Lee, S., Lee, B., Lee, J. W. & Lee, S.-K. The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes Dev.21, 744–749 (2007). CASPubMedPubMed Central Google Scholar
Yoo, A. S., Staahl, B. T., Chen, L. & Crabtree, G. R. MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature460, 642–646 (2009). CASPubMedPubMed Central Google Scholar
Makeyev, E. V., Zhang, J., Carrasco, M. A. & Maniatis, T. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol. Cell27, 435–448 (2007). CASPubMedPubMed Central Google Scholar
Boutz, P. L., Chawla, G., Stoilov, P. & Black, D. L. MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes Dev.21, 71–84 (2007). CASPubMedPubMed Central Google Scholar
Chen, J. F. et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nature Genet.38, 228–233 (2006). CASPubMed Google Scholar
Zhao, Y., Samal, E. & Srivastava, D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature436, 214–220 (2005). CASPubMed Google Scholar
Zhao, Y. et al. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell129, 303–317 (2007). CASPubMed Google Scholar
Zhao, C., Sun, G., Li, S. & Shi, Y. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. Nature Struct. Mol. Biol.16, 365–371 (2009). CAS Google Scholar
Clark, A. et al. The microRNA miR-124 controls gene expression in the sensory nervous system of Caenorhabditis elegans. Nucleic Acids Res.38, 3780–3793 (2010). CASPubMedPubMed Central Google Scholar
Johnston, R. J. & Hobert, O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature426, 845–849 (2003). One of the first studies that implicated miRNAs in regulating cell fate decisions. CASPubMed Google Scholar
Johnston, R. J. & Hobert, O. A novel C. elegans zinc finger transcription factor, lsy-2, required for the cell type-specific expression of the lsy-6 microRNA. Development132, 5451–5460 (2005). CASPubMed Google Scholar
Didiano, D., Cochella, L., Tursun, B. & Hobert, O. Neuron-type specific regulation of a 3′UTR through redundant and combinatorially acting _cis_-regulatory elements. RNA16, 349–363 (2010). CASPubMedPubMed Central Google Scholar
Ponjavic, J., Oliver, P. L., Lunter, G. & Ponting, C. P. Genomic and transcriptional co-localization of protein-coding and long non-coding RNA pairs in the developing brain. PLoS Genet.5, e1000617 (2009). PubMedPubMed Central Google Scholar
Mercer, T. R., Dinger, M. E., Sunkin, S. M., Mehler, M. F. & Mattick, J. S. Specific expression of long noncoding RNAs in the mouse brain. Proc. Natl Acad. Sci. USA105, 716–721 (2008). CASPubMedPubMed Central Google Scholar
Young, T. L., Matsuda, T. & Cepko, C. L. The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr. Biol.15, 501–512 (2005). CASPubMed Google Scholar
Feng, J. et al. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes Dev.20, 1470–1484 (2006). CASPubMedPubMed Central Google Scholar
Schratt, G. M. et al. A brain-specific microRNA regulates dendritic spine development. Nature439, 283–289 (2006). CASPubMed Google Scholar
Korpal, M., Lee, E. S., Hu, G. & Kang, Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J. Biol. Chem.283, 14910–14914 (2008). CASPubMedPubMed Central Google Scholar
Park, S.-M., Gaur, A. B., Lengyel, E. & Peter, M. E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev.22, 894–907 (2008). CASPubMedPubMed Central Google Scholar
Gregory, P. A. et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biol.10, 593–601 (2008). References 141–143 identify the miR-200 family as essential regulators of the gene regulatory network that guards the EMT. These studies also indicate that misregulation of pathways that are normally active during development can cause disease during later stages of development. CASPubMed Google Scholar
Rajasethupathy, P. et al. Characterization of small RNAs in Aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB. Neuron63, 803–817 (2009). CASPubMedPubMed Central Google Scholar
Thiery, J. P., Acloque, H., Huang, R. Y. J. & Nieto, M. A. Epithelial-mesenchymal transitions in development and disease. Cell139, 871–890 (2009). CASPubMed Google Scholar
Cano, A. & Nieto, M. A. Non-coding RNAs take centre stage in epithelial-to-mesenchymal transition. Trends Cell Biol.18, 357–359 (2008). CASPubMed Google Scholar
Burk, U. et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep.9, 582–589 (2008). CASPubMedPubMed Central Google Scholar
Wellner, U. et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nature Cell Biol.11, 1487–1495 (2009). CASPubMed Google Scholar
Beltran, M. et al. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev.22, 756–769 (2008). CASPubMedPubMed Central Google Scholar
Frankel, L. B. et al. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J. Biol. Chem.283, 1026–1033 (2008). CASPubMed Google Scholar
Asangani, I. A. et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene27, 2128–2136 (2008). CASPubMed Google Scholar
Davis, B. N., Hilyard, A. C., Lagna, G. & Hata, A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature454, 56–61 (2008). CASPubMedPubMed Central Google Scholar
Davis, B. N., Hilyard, A. C., Nguyen, P. H., Lagna, G. & Hata, A. Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha. Mol. Cell39, 373–384 (2010). CASPubMedPubMed Central Google Scholar
Miska, E. A. et al. Most Caenorhabditis elegans microRNAs are individually not essential for development or viability. PLoS Genet.3, e215 (2007). PubMedPubMed Central Google Scholar
Abbott, A. L. et al. The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. Dev. Cell9, 403–414 (2005). CASPubMedPubMed Central Google Scholar
Grimson, A. et al. Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature455, 1193–1197 (2008). CASPubMed Google Scholar
Christodoulou, F. et al. Ancient animal microRNAs and the evolution of tissue identity. Nature463, 1084–1088 (2010). CASPubMedPubMed Central Google Scholar
Clop, A. et al. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nature Genet.38, 813–818 (2006). CASPubMed Google Scholar
Hanyu-Nakamura, K., Sonobe-Nojima, H., Tanigawa, A., Lasko, P. & Nakamura, A. Drosophila Pgc protein inhibits P-TEFb recruitment to chromatin in primordial germ cells. Nature451, 730–733 (2008). CASPubMedPubMed Central Google Scholar
Kondo, T. et al. Small peptides switch the transcriptional activity of shavenbaby during Drosophila embryogenesis. Science329, 336–339 (2010). CASPubMed Google Scholar
Kondo, T. et al. Small peptide regulators of actin-based cell morphogenesis encoded by a polycistronic mRNA. Nature Cell Biol.9, 660–665 (2007). CASPubMed Google Scholar
Candeias, M. M. et al. P53 mRNA controls p53 activity by managing Mdm2 functions. Nature Cell Biol.10, 1098–1105 (2008). CASPubMed Google Scholar
Jenny, A. et al. A translation-independent role of oskar RNA in early Drosophila oogenesis. Development133, 2827–2833 (2006). CASPubMed Google Scholar
Iliopoulos, D. et al. Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells. Mol. Cell39, 761–772 (2010). CASPubMedPubMed Central Google Scholar
Shimono, Y. et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell138, 592–603 (2009). CASPubMedPubMed Central Google Scholar
Lee, J. T. The X as model for RNA's niche in epigenomic regulation. Cold Spring Harb. Perspect. Biol.2, a003749 (2010). PubMedPubMed Central Google Scholar
Cheng, L.-C., Pastrana, E., Tavazoie, M. & Doetsch, F. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nature Neurosci.12, 399–408 (2009). CASPubMed Google Scholar