Abstract
microRNAs (miRNAs) and small interfering RNAs (siRNAs) play important roles in gene regulation and defense responses against transposons and viruses in eukaryotes. These small RNAs generally trigger the silencing of cognate sequences through a variety of mechanisms, including RNA degradation, translational inhibition and transcriptional repression. In the past few years, the synthesis and the mode of action of miRNAs and siRNAs have attracted great attention. However, relatively little is known about mechanisms of quality control during small RNA biogenesis as well as those that regulate mature small RNA stability. Recent studies in Arabidopsis thaliana and Caenorhabditis elegans have implicated 3′-to-5′ (SDNs) and 5′-to-3′ (XRN-2) exoribonucleases in mature miRNA turnover and the modulation of small RNA levels and activity. In the green alga Chlamydomonas reinhardtii, a nucleotidyltransferase (MUT68) and an exosome subunit (RRP6) are involved in the 3′ untemplated uridylation and the degradation of miRNAs and siRNAs. The latter enzymes appear to function as a quality control mechanism to eliminate putative dysfunctional or damaged small RNA molecules. Several post-transcriptional modifications of miRNAs and siRNAs such as 3′ terminal methylation and untemplated nucleotide additions have also been reported to affect small RNA stability. These collective findings are beginning to uncover a new layer of regulatory control in the pathways involving small RNAs. We anticipate that understanding the mechanisms of mature miRNA and siRNA turnover will have direct implications for fundamental biology as well as for applications of RNA interference technology.
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References
Ghildiyal M, Zamore PD. Small silencing RNAs: an expanding universe. Nat Rev Genet 2009; 10:94–108.
Carthew RW, Sontheimer EJ. Silence from within: endogenous siRNAs and miRNAs. Cell 2009; 136:642–655.
Baulcombe D. RNA silencing in plants. Nature 2004; 431:356–363.
Cerutti H, Casas-Mollano JA. On the origin and functions of RNA-mediated silencing: from protists to man. Curr Genet 2006; 50:81–99.
Voinnet O. Origin, biogenesis and activity of plant microRNAs. Cell 2009; 136:669–687.
Chen X. Small RNAs and their roles in plant development. Annu Rev Cell Dev Biol 2009; 35:21–44.
Chapman EJ, Carrington JC. Specialization and evolution of endogenous small RNA pathways. Nat Rev Genet 2007; 8:884–896.
Steitz JA, Vasudevan S. miRNPs: versatile regulators of gene expression in vertebrate cells. Biochem Soc Trans 2009; 37:931–935.
Molnár A, Schwach F, Studholme DJ et al. miRNAs control gene expression in the single-cell alga Chlamydomonas reinhardtii. Nature 2007; 447:1126–1129.
Zhao T, Li G, Mi S et al. A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii. Genes Dev 2007; 21:1190–1203.
Casas-Mollano JA, Rohr J, Kim EJ et al. Diversification of the core RNA interference machinery in Chlamydomonas reinhardtii and the role of DCL1 in transposon silencing. Genetics 2008; 179:69–81.
De Riso V, Raniello R, Maumus F et al. Gene silencing in the marine diatom Phaeodactylum tricornutum. Nucleic Acids Res 2009; 37:e96.
Ramachandran V, Chen X, Small RNA metabolism in Arabidopsis. Trends Plant Sci 2008; 13:368–374.
Yuan YR, Pei Y, Ma JB et al. Crystal structure of A. aeolicus argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage. Mol Cell 2005; 19:405–419.
Wang Y, Juranek S, Li H et al. Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes. Nature 2009; 461:754–761.
Kawamata T, Seitz H, Tomari Y. Structural determinants of miRNAs for RISC loading and slicer-independent unwinding. Nat Struct Mol Biol 2009; 16:953–960.
Winter J, Jung S, Keller S et al. Many roads to maturity: microRNA biogenesis pathways and theirregulation. Nat Cell Biol 2009; 11:228–234.
Wilusz CJ, Wilusz J. Bringing the role of mRNA decay in the control of gene expression into focus. Trends Genet 2004; 20:491–497.
Isken O, Maquat LE. Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. Genes Dev 2007; 21:1833–1856.
Okada C, Yamashita E, Lee S J et al. A high-resolution structure of the pre-microRNA nuclear export machinery. Science 2009; 326:1275–1279.
Fang Y, Spector DL. Identification of nuclear dicing bodies containing proteins for miRNA biogenesis in living Arabidopsis plants. Curr Biol 2007; 17:818–823.
Song L, Han MH, Lesicka J et al. Arabidopsis primary microRNA processing proteins HYL1 and DCL1 define a molecular body distinct from the Cajal body. Proc Natl Acad Sci USA 2007; 104:5437–5442.
Fujioka Y, Utsumi M, Ohba Y et al. Location of a possible miRNA processing site in SmD3/SmB nuclear bodies in Arabidopsis. Plant Cell Physiol 2007; 48:1243–1253.
Michlewski G, Guil S, Semple CA et al. Post-transcriptional regulation of miRNAs harboring conserved terminal loops. Mol Cell 2008; 32:383–393.
Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of microRNA processing by Lin28. Science 2009; 320:97–100.
Trabucchi M, Briata P, Garcia-Mayoral M et al. The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 2009; 459:1010–1014.
Yamagata K, Fujiyama S, Ito S et al. Maturation of microRNA is hormonally regulated by a nuclear receptor. Mol Cell 2009; 36:340–347.
Heo I, Joo C, Kim Y-K et al. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell 2009; 138:696–708.
Hagan JP, Piskounova E, Gregory RI. Lin28 recruits the TUTase Zcchcl 1 to inhibit let-7 maturation in mouse embryonic stem cells. Nat Struct Mol Biol 2009; 16:1021–1025.
Lehrbach NJ, Armisen J, Lightfoot HL et al. LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans. Nat Struct Mol Biol 2009; 16:1016–1020.
Nogueira F, Chitwood D, Madi S et al. Regulation of small RNA accumulation in the maize shoot apex. PLoS Genet 2009; 5:el000320.
Yu B, Yang Z, Li J et al. Methylation as a crucial step in plant microRNA biogenesis. Science 2005; 307:932–935.
Ibrahim F, Rymarquis LA, Kim E-J et al. Uridylation of mature miRNAs and siRNAs by the MUT68 nucleotidyltransferase promotes their degradation in Chlamydomonas. Proc Natl Acad Sci USA 2010; 107:3906–3911.
Yang Z, Ebright YW, Yu B et al. HENl recognizes 21–24 nt small RNA duplexes and deposits a methyl group onto the 2′ OH of the 3′ terminal nucleotide. Nucleic Acids Res 2006; 34:667–675.
Huang Y, Ji L, Huang Q et al. Structural insights into mechanisms of the small RNA methyltransferase HENl. Nature 2009; 461:823–827.
Yu B, Chapman EJ, Yang Z et al. Transgenically expressed viral RNA silencing suppressors interfere with microRNA methylation in Arabidopsis. FEBS Lett 2006; 580:3117–3120.
Farazi TA, Juranek SA, Tuschl T. The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members. Development 2008; 135:1201–1214.
Horwich MD, Li C, Matranga C et al. The Drosophila RNA methyltransferase, DmHen 1, modifies germline piRNAs and single-stranded siRNAs in RISC. Curr Biol 2007; 17:1265–1272.
Saito K, Sakaguchi Y, Suzuki T et al. Pimet, the Drosophila homolog of HENl, mediates 2′-0-methylation of Piwi-interacting RNAs at their 3′ ends. Genes Dev 2007; 21:1603–1608.
Kirino Y, Mourelatos Z. The mouse homolog of HENl is a potential methylase for Piwi-interacting RNAs. RNA 2007; 13:1397–1401.
Okamura K, Liu N, Lai EC. Distinct mechanisms for microRNA strand selection by Drosophila argonautes. Mol Cell 2009; 36:431–444.
Czech B, Zhou R, Erlich Y et al. Hierarchical rules for argonaute loading in Drosophila. Mol Cell 2009; 36:445–456.
Ghildiyal M, Xu J, Seitz H et al. Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. RNA 2010; 16:43–56.
Li J, Yang Z, Yu B et al. Methylation protects miRNAs and siRNAs from a 3′-end uridylation activity in Arabidopsis. Curr Biol 2005; 15:1501–1507.
Kurth HM, Mochizuki K. 2′-0-methylation stabilizes piwi-associated small RNAs and ensures DNA elimination in Tetrahymena. RNA 2009; 15:675–685.
Liu Y, Ye X, Jiang F et al. C3PO, an endoribonuclease that promotes RNAi by facilitating RISC activation. Science 2009; 325:750–753.
Wang B, Li S, Qi HH et al. Distinct passenger strand and mRNA cleavage activities of human argonaute proteins. Nat Struct Mol Biol 2009; 16:1259–1266.
Kim K, Lee YS, Carthew RW. Conversion of preRISC to holo-RISC by Ago2 during assembly of RNAi complexes. RNA 2007; 13:22–29.
Schwarz DS, Hutvagner G, Du T et al. Asymmetry in the assembly of the RNAi enzyme complex. Cell 2003; 115:199–208.
Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs exhibit strand bias. Cell 2003; 115:209–216.
Eamens AL, Smith NA, Curtin SJ et al. The Arabidopsis thaliana double-stranded RNA binding protein DRB1 directs guide strand selection from microRNA duplexes. RNA 2009; 15:2219–2235.
Ro S, Park C, Young D et al. Tissue-dependent paired expression of miRNAs. Nucleic Acids Res 2007; 35:5944–5953.
Wei J-X, Yang J, Sun J-F et al. Both strands of siRNA have potential to guide post-transcriptional gene silencing in mammalian cells. PLoS ONE 2009; 4:e5382.
Vaucheret H. Plant ARGONAUTES. Trends Plant Sci 2008; 13:350–358.
Li CF, Pontes O, El-Shami M et al. An ARGONAUTE4-containing nuclear processing center colocalized with Cajal bodies in Arabidopsis thaliana. Cell 2006; 126:93–106.
Mi S, Cai T, Hu Y et al. Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5′ terminal nucleotide. Cell 2008; 133:116–127.
Takeda A, Iwasaki S, Watanabe T et al. The mechanism selecting the guide strand from small RNA duplexes is different among argonaute proteins. Plant Cell Physiol 2008; 49:493–500.
Qi Y, Denli AM, Hannon GJ. Biochemical specialization within Arabidopsis RNA silencing pathways. Mol Cell 2005; 19:421–428.
Montgomery TA, Howell MD, Cuperus JT et al. Specificity of ARGONAUTE7-miR390 interaction and dual functionality in TAS3 trans-acting siRNA formation. Cell 2008; 133:128–141.
Park MY, Wu G, Gonzalez-Sulser A et al. Nuclear processing and export of microRNAs in Arabidopsis. Proc Natl Acad Sci USA 2005; 102:3691–3696.
Han MH, Goud S, Song L et al. The Arabidopsis double-stranded RNA-binding protein HYL1 plays a role in microRNA-mediated gene regulation. Proc Natl Acad Sci USA 2004; 101:1093–1098.
Weinmann L, Hock J, Ivacevic T et al. Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell 2009; 136:496–507.
Castanotto D, Lingeman R, Riggs AD et al. CRM1 mediates nuclear-cytoplasmic shuttling of mature microRNAs. Proc Natl Acad. Sci USA 2009; 106:21655–59.
Ramachandran V, Chen X. Degradation of microRNAs by a family of exoribonucleases in Arabidopsis. Science 2008; 321:1490–1492.
Kennedy S, Wang D, Ruvkun G A conserved siRNA-degradingRNase negatively regulates RNA interference in C. elegans. Nature 2004; 427:645–649.
Iida T, Kawaguchi R, Nakayama J. Conserved ribonuclease, Eril, negatively regulates heterochromatin assembly in fission yeast. Curr Biol 2006; 16:1459–1464.
Duchaine TF, Wohlschlegel JA, Kennedy S et al. Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in multiple small-RNA-mediated pathways. Cell 2006; 124:343–354.
Gabel HW, Ruvkun G The exonuclease ERI-1 has a conserved dual role in 5.8S rRNA processing and RNAi. Nat Struct Mol Biol 2008; 15:531–533.
Chatterjee S, Großhans H. Active turnover modulates mature microRNA activity in Caenorhabditis elegans. Nature 2009; 461:546–549.
Mullen TE, Marzluff WF. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5′ to 3′ and 3′ to 5′. Genes Dev 2008; 22:50–65.
Wilusz CJ, Wilusz J. New ways to meet your (3′) end—oligouridylation as a step on the path to destruction. Genes Dev 2008; 22:1–7.
Zimmer SL, Fei Z, Stern DB. Genome-based analysis of Chlamydomonas reinhardtii exoribonucleases and poly(A) polymerases predicts unexpected organellar and exosomal features. Genetics 2008; 179:125–136.
Gy I, Gasciolli V, Lauressergues D et al. Arabidopsis FIERY 1, XRN2 and XRN3 are endogenous RNA silencing suppressors. Plant Cell 2007; 19:3451–3461.
Ibrahim F, Rohr J, Jeong WJ et al. Untemplated oligoadenylation promotes degradation of RISC-cleaved transcripts. Science 2006; 314:1893.
Schmid M, Jensen TH. The exosome: a multipurpose RNA-decay machine. Trends Biochem Sci 2008; 33:501–510.
Belostotsky D. Exosome complex and pervasive transcription in eukaryotic genomes. Curr Opin Cell Biol 2009; 21:352–358.
Zuo Y, Deutscher MP. Exoribonuclease superfamilies: structural analysis and phylogenetic distribution. Nucleic Acids Res 2001; 29:1017–1026.
Nagaike T, Suzuki T, Katoh T et al. Human mitochondrial mRNAs are stabilized with polyadenylation regulated by mitochondria-specific poly(A) polymerase and polynucleotide Phosphorylase. J Biol Chem 2005; 280:19721–7.
Rissland OS, Mikulaslova A, Norbury CJ. Efficient RNA polyuridylation by noncanonical poly(A) polymerases. Mol Cell Biol 2007; 27:3612–3624.
Katoh T, Sakaguchi Y, Miyauchi K et al. Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Genes Dev 2009; 23:433–438.
Lu S, Sun Y-H, Chiang VL. Adenylation of plant miRNAs. Nucleic Acids Res 2009; 37:1878–1885.
Lange H, Holec S, Cognat V et al. Degradation of a polyadenylated rRNA maturation by-product involves one of the three RRP6-like proteins in Arabidopsis thaliana. Mol Cell Biol 2008; 28:3038–3044.
Zhou R, Hotta I, Denli AM et al. Comparative analysis of Argonaute-dependent small RNA pathways in Drosophila. Mol Cell 2008; 32:592–599.
van Wolfswinkel JC, Claycomb JM, Batista PJ et al. CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs. Cell 2009; 139:135–148.
Felice KM, Salzman DW, Shubert-Coleman J et al. The 5′ terminal uracil of let-7a is critical for the recruitment of mRNA to Argonaute2. Biochem J 2009; 422:329–341.
Ebhardt HA, Tsang HH, Dai DC et al. Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications. Nucleic Acids Res 2009; 37:2461–2470.
Haley B, Zamore PD. Kinetic analysis of the RNAi enzyme complex. Nat Struct Mol Biol 2004; 11:599–606.
Jinek M, Doudna JA. A three-dimensional view of the molecular machinery of RNA interference. Nature 2009; 457:405–412.
Orban TI, Izaurralde E. Decay of mRNAs targeted by RISC requires XRN1, the Ski complex and the exosome. RNA 2005; 11:459–469.
Souret FF, Kastenmayer JP, Green PJ. AtXRN4 degrades mRNA in Arabidopsis and its substrates include selected miRNA targets. Mol Cell 2004; 15:173–183.
Kai ZS, Pasquinelli AE. microRNA assassins: factors that regulate the disappearance of miRNAs. Nat Struct Mol Biol 2010; 17:5–10.
Hwang H-W, Wentzel EA, Mendell JT. A hexanucleotide element directs microRNA nuclear import. Science 2007; 315:97–100.
Jones MR, Quintan LJ, Blahna MT et al. Zcchcl 1-dependent uridylation of microRNA directs cytokine expression. Nat Cell Biol 2009; 11:1157–1163.
LaCava J, Houseley J, Saveanu C et al. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 2005; 121:713–724.
Wyers F, Rougemaille M, Badis G et al. Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 2005; 121:725–737.
Vanacova S, Wolf J, Martin G et al. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol 2005; 3:el89.
Ma J-B, Ye K, Patel DJ. Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature 2004; 429:318–322.
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Cerutti, H., Ibrahim, F. (2010). Turnover of Mature miRNAs and siRNAs in Plants and Algae. In: Großhans, H. (eds) Regulation of microRNAs. Advances in Experimental Medicine and Biology, vol 700. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7823-3_11
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DOI: https://doi.org/10.1007/978-1-4419-7823-3_11
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