MicroRNA rules: Made to be broken

Abstract

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression. For over a decade the deluge of research describing the biogenesis and activity of miRNAs has lead researchers to postulate rules to help make sense of the enormous amount of data produced. These rules are repeated in miRNA research papers and reviews. While these rules have been helpful one must be conscious of their limitations or risk missing future breakthroughs. Here we describe some of the most commonly stated rules, the reasoning behind their formation, their uses, and limitations.

Keywords

microRNA / post-transcriptional / gene regulation / mRNA / 3' UTR / conservation rule / seed pairing rule / biogenesis rule / mechanism of action rule

References

[1] Alexiou P, Maragkakis M, Papadopoulos G L, Reczko M, Hatzigeorgiou A G (2009). Lost in translation: an assessment and perspective for computational microRNA target identification. Bioinformatics, 25(23): 3049-3055

[2] Baek D, Villén J, Shin C, Camargo F D, Gygi S P, Bartel D P (2008). The impact of microRNAs on protein output. Nature, 455(7209): 64-71

[3] Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R, Pasquinelli A E (2005). Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell, 122(4): 553-563

[4] Bartel D P (2009). MicroRNAs: target recognition and regulatory functions. Cell, 136(2): 215-233

[5] Bazzini A A, Lee M T, Giraldez A J (2012). Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish. Science, 336(6078): 233-237

[6] Behm-Ansmant I, Rehwinkel J, Doerks T, Stark A, Bork P, Izaurralde E (2006). mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev, 20(14): 1885-1898

[7] Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, Sharon E, Spector Y, Bentwich Z (2005). Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet, 37(7): 766-770

[8] Berezikov E, van Tetering G, Verheul M, van de Belt J, van Laake L, Vos J, Verloop R, van de Wetering M, Guryev V, Takada S, van Zonneveld A J, Mano H, Plasterk R, Cuppen E (2006). Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis. Genome Res, 16(10): 1289-1298

[9] Brennecke J, Stark A, Cohen S M (2005). Not miR-ly muscular: microRNAs and muscle development. Genes Dev, 19(19): 2261-2264

[10] Carthew R W, Sontheimer E J (2009). Origins and mechanisms of miRNAs and siRNAs. Cell, 136(4): 642-655

[11] Chi S W, Zang J B, Mele A, Darnell R B (2009). Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature, 460(7254): 479-486

[12] D'Alessio G, Riordan J F (1997) Ribonucleases: Structures and Functions. Academic Press, New York, NY

[13] Djuranovic S, Nahvi A, Green R (2012). miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay. Science, 336(6078): 237-240

[14] Elbashir S M, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411(6836): 494-498

[15] Elefant N, Altuvia Y, Margalit H (2011). A wide repertoire of miRNA binding sites: prediction and functional implications. Bioinformatics, 27(22): 3093-3101

[16] Elkayam E, Kuhn C D, Tocilj A, Haase A D, Greene E M, Hannon G J, Joshua-Tor L (2012). The structure of human argonaute-2 in complex with miR-20a. Cell, 150(1): 100-110

[17] Friedman R C, Farh K K, Burge C B, Bartel D P (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Res, 19(1): 92-105

[18] Giraldez A J, Mishima Y, Rihel J, Grocock R J, Van Dongen S, Inoue K, Enright A J, Schier A F (2006). Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science, 312(5770): 75-79

[19] Grimson A, Farh K K, Johnston W K, Garrett-Engele P, Lim L P, Bartel D P (2007). MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell, 27(1): 91-105

[20] Gu S, Jin L, Zhang F, Sarnow P, Kay M A (2009). Biological basis for restriction of microRNA targets to the 3′ untranslated region in mammalian mRNAs. Nat Struct Mol Biol, 16(2): 144-150

[21] Guo H, Ingolia N T, Weissman J S, Bartel D P (2010). Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature, 466(7308): 835-840

[22] Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M Jr, Jungkamp A C, Munschauer M, Ulrich A, Wardle G S, Dewell S, Zavolan M, Tuschl T (2010). Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell, 141(1): 129-141

[23] Hendrickson D G, Hogan D J, McCullough H L, Myers J W, Herschlag D, Ferrell J E, Brown P O (2009). Concordant regulation of translation and mRNA abundance for hundreds of targets of a human microRNA. PLoS Biol, 7(11): e1000238

[24] Jopling C L, Yi M, Lancaster A M, Lemon S M, Sarnow P (2005). Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science, 309(5740): 1577-1581

[25] Kim V N, Han J, Siomi M C (2009). Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol, 10(2): 126-139

[26] Krol J, Krzyzosiak W J (2004). Structural aspects of microRNA biogenesis. IUBMB Life, 56(2): 95-100

[27] Krol J, Loedige I, Filipowicz W (2010). The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet, 11(9): 597-610

[28] Krützfeldt J, Rajewsky N, Braich R, Rajeev K G, Tuschl T, Manoharan M, Stoffel M (2005). Silencing of microRNAs in vivo with ‘antagomirs’. Nature, 438(7068): 685-689

[29] Lee R C, Feinbaum R L, Ambros V (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75(5): 843-854

[30] Lee S, Vasudevan S (2013). Post-transcriptional stimulation of gene expression by microRNAs. Adv Exp Med Biol, 768: 97-126

[31] Lewis B P, Shih I H, Jones-Rhoades M W, Bartel D P, Burge C B (2003). Prediction of mammalian microRNA targets. Cell, 115(7): 787-798

[32] Lim L P, Lau N C, Weinstein E G, Abdelhakim A, Yekta S, Rhoades M W, Burge C B, Bartel D P (2003). The microRNAs of Caenorhabditis elegans. Genes Dev, 17(8): 991-1008

[33] Llave C, Xie Z, Kasschau K D, Carrington J C (2002). Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science, 297(5589): 2053-2056

[34] Machlin E S, Sarnow P, Sagan S M (2011). Masking the 5′ terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex. Proc Natl Acad Sci USA, 108(8): 3193-3198

[35] Mayr C, Bartel D P (2009). Widespread shortening of 3’UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell, 138(4): 673-684

[36] Mitchell P S, Parkin R K, Kroh E M, Fritz B R, Wyman S K, Pogosova-Agadjanyan E L, Peterson A, Noteboom J, O’Briant K C, Allen A, Lin D W, Urban N, Drescher C W, Knudsen B S, Stirewalt D L, Gentleman R, Vessella R L, Nelson P S, Martin D B, Tewari M (2008). Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA, 105(30): 10513-10518

[37] Miyoshi K, Miyoshi T, Siomi H (2010). Many ways to generate microRNA-like small RNAs: non-canonical pathways for microRNA production. Mol Genet Genomics, 284(2): 95-103

[38] Nguyen H T, Frasch M (2006). MicroRNAs in muscle differentiation: lessons from Drosophila and beyond. Curr Opin Genet Dev, 16(5): 533-539

[39] Olsen P H, Ambros V (1999). The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol, 216(2): 671-680

[40] Pasquinelli A E, McCoy A, Jiménez E, Saló E, Ruvkun G, Martindale M Q, Baguñà J (2003). Expression of the 22 nucleotide let-7 heterochronic RNA throughout the Metazoa: a role in life history evolution? Evol Dev, 5(4): 372-378

[41] Pasquinelli A E, Reinhart B J, Slack F, Martindale M Q, Kuroda M I, Maller B, Hayward D C, Ball E E, Degnan B, Müller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature, 408(6808): 86-89

[42] Rehwinkel J, Behm-Ansmant I, Gatfield D, Izaurralde E (2005). A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. RNA, 11(11): 1640-1647

[43] Reinhart B J, Slack F J, Basson M, Pasquinelli A E, Bettinger J C, Rougvie A E, Horvitz H R, Ruvkun G (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature, 403(6772): 901-906

[44] Roush S, Slack F J (2008). The let-7 family of microRNAs. Trends Cell Biol, 18(10): 505-516

[45] Sandberg R, Neilson J R, Sarma A, Sharp P A, Burge C B (2008). Proliferating cells express mRNAs with shortened 3′ untranslated regions and fewer microRNA target sites. Science, 320(5883): 1643-1647

[46] Schirle N T, MacRae I J (2012). The crystal structure of human Argonaute2. Science, 336(6084): 1037-1040

[47] Schnall-Levin M, Rissland O S, Johnston W K, Perrimon N, Bartel D P, Berger B (2011). Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs. Genome Res, 21(9): 1395-1403

[48] Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (2008). Widespread changes in protein synthesis induced by microRNAs. Nature, 455(7209): 58-63

[49] Shin C, Nam J W, Farh K K, Chiang H R, Shkumatava A, Bartel D P (2010). Expanding the microRNA targeting code: functional sites with centered pairing. Mol Cell, 38(6): 789-802

[50] Sokol N S, Ambros V (2005). Mesodermally expressed Drosophila microRNA-1 is regulated by Twist and is required in muscles during larval growth. Genes Dev, 19(19): 2343-2354

[51] Sun J, Gao B, Zhou M, Wang Z Z, Zhang F, Deng J E, Li X (2013). Comparative genomic analysis reveals evolutionary characteristics and patterns of microRNA clusters in vertebrates. Gene, 512(2): 383-391

[52] Tsui N B, Ng E K, Lo Y M (2002). Stability of endogenous and added RNA in blood specimens, serum, and plasma. Clin Chem, 48(10): 1647-1653

[53] Wang Y, Sheng G, Juranek S, Tuschl T, Patel D J (2008). Structure of the guide-strand-containing argonaute silencing complex. Nature, 456(7219): 209-213

[54] Weber J A, Baxter D H, Zhang S, Huang D Y, Huang K H, Lee M J, Galas D J, Wang K (2010). The microRNA spectrum in 12 body fluids. Clin Chem, 56(11): 1733-1741

[55] Wen M, Shen Y, Shi S, Tang T (2012). miREvo: an integrative microRNA evolutionary analysis platform for next-generation sequencing experiments. BMC Bioinformatics, 13(1): 140

[56] Wightman B, Ha I, Ruvkun G (1993). Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell, 75(5): 855-862

[57] Williamson V, Kim A, Xie B, McMichael G O, Gao Y, Vladimirov V (2013). Detecting miRNAs in deep-sequencing data: a software performance comparison and evaluation. Brief Bioinform, 14(1): 36-45

[58] Wu L, Fan J, Belasco J G (2006). MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci USA, 103(11): 4034-4039

[59] Yang J S, Lai E C (2011). Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants. Mol Cell, 43(6): 892-903

[60] Yekta S, Shih I H, Bartel D P (2004). MicroRNA-directed cleavage of HOXB8 mRNA. Science, 304(5670): 594-596

[61] Zamore P D, Tuschl T, Sharp P A, Bartel D P (2000). RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell, 101(1): 25-33

[62] Zhang R, Wang Y Q, Su B (2008). Molecular evolution of a primate-specific microRNA family. Mol Biol Evol, 25(7): 1493-1502

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg