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microRNA Timeline

Timeline Who What Organism Reference
1960s Britten RJ and Davidson EH Proposed that "activator" RNAs transcribed from redundant genomic regions form complexes with regulatory DNA sequences to activate a battery of protein coding genes. Eukaryotes Britten RJ, Davidson EH. Gene regulation for higher cells: a theory  Science. 1969 Jul 25;165(891):349-57.
1993 Ambros  Lab
Ruvkun Lab
Discovered the first microRNA, lin-4 C. elegans Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993 Dec 3;75(5):843-54.
Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993 Dec 3;75(5):855-62.
2000 Ruvkun Lab Discovered let-7 microRNA C. elegans Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans.
Nature. 2000 Feb 24;403(6772):901-6.
2001 Bartel Lab
Tuschl Lab
Ambros Lab
Discovered a large class of small RNAs with potential regulatory roles and named them microRNA (miRNA) C. elegans,
nvertebrates, and vertebrates
Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.
Science. 2001 Oct 26;294(5543):858-62.
Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001 Oct 26;294(5543):853-8.
Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science. 2001 Oct 26;294(5543):862-4.


Bartel Lab Discovered microRNA in plants Plants Reinhart BJ, Weinstein EG, Rhoades MW, Bartel B, Bartel DP. MicroRNAs in plants. Genes Dev. 2002 Jul 1;16(13):1616-26.
Rhoades MW, Reinhart BJ, Lim LP, Burge CB, Bartel B, Bartel DP. Prediction of plant microRNA targets. Cell. 2002 Aug 23;110(4):513-20.
2002 Croce Lab Showed that miRNAs are implicated in cancer based on the observation that miR15 and miR16 are deleted or downregulated in most chronic lymphocytic leukemias. Human Calin GA, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524-9.
2003 Stoffel Lab Silenced miRNAs in vivo using chemically engineered oligonucleotides, termed 'antagomirs', Mammals Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. Silencing of microRNAs in vivo with 'antagomirs'. Nature. 2005 Dec 1;438(7068):685-9.
2007 Vasudevan S et al. First demonstrated that miRNA could activation mRNA translation Human Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007 Dec 21;318(5858):1931-4. Epub 2007 Nov 29.
2008 Place R, et al. First reported miRNA-mediated transcriptional gene activation. Human Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R. MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1608-13. Epub 2008 Jan 28.
2008 Kim DH, et al First reported miRNA-induced transcriptional gene silencing.  Human Kim DH, Saetrom P, SnÝve O Jr, Rossi JJ. MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16230-5. Epub 2008 Oct 13.
2012 Zhang L, et al First reported the detection of food-derived exogenous miRNAs in serum and plasma of animals and cross-kingdom regulation of a mouse gene by a plant miRNA.  Human and Mouse Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q, Chen J, Wang J, Wang M, Zhang Q, Zhang J, Zen K, Zhang CY. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res. 2012 Jan;22(1):107-26.

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