MicroRNA biogenesis: Epigenetic modifications as another layer of complexity in the microRNA expression regulation.

Since their discovery, microRNAs have led to a huge shift in our understanding of the regulation of key biological processes. The discovery of epigenetic modifications that affect microRNA expression has added another layer of complexity to the already tightly controlled regulatory machinery. Modifications like uridylation, adenylation and RNA editing have been shown to have variable effects on miRNA biogenesis and action. Methylation of the N6 adenosine has been studied extensively in mRNA. Presence of the N6-methyl-adenosine (m6A) mark and its critical importance in miRNA biogenesis in animals adds to our understanding of the regulatory mechanisms, while its effect on miRNA biogenesis in plants is yet to be understood.

[1]  E. Izaurralde,et al.  Getting to the Root of miRNA-Mediated Gene Silencing , 2008, Cell.

[2]  Bernd Mueller-Roeber,et al.  Gene structures and processing of Arabidopsis thaliana HYL1-dependent pri-miRNAs , 2009, Nucleic acids research.

[3]  B. Berger,et al.  Conserved microRNA targeting in Drosophila is as widespread in coding regions as in 3′UTRs , 2010, Proceedings of the National Academy of Sciences.

[4]  Xuemei Chen,et al.  Uridylation of miRNAs by HEN 1 SUPPRESSOR 1 in Arabidopsis , 2017 .

[5]  Peter M. Waterhouse,et al.  Plant and animal microRNAs: similarities and differences , 2005, Functional & Integrative Genomics.

[6]  G. Ruvkun,et al.  Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans , 1993, Cell.

[7]  D. Baulcombe,et al.  Arabidopsis ARGONAUTE1 is an RNA Slicer that selectively recruits microRNAs and short interfering RNAs. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Martin Crespi,et al.  Plant polycistronic precursors containing non-homologous microRNAs target transcripts encoding functionally related proteins , 2009, Genome Biology.

[9]  Guifang Jia,et al.  Reversible RNA adenosine methylation in biological regulation. , 2013, Trends in genetics : TIG.

[10]  Elisa Izaurralde,et al.  Deadenylation is a widespread effect of miRNA regulation. , 2008, RNA.

[11]  Yu Li,et al.  MicroRNAs in Common Human Diseases , 2012, Genom. Proteom. Bioinform..

[12]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

[13]  T. Katoh,et al.  Selective stabilization of mammalian microRNAs by 3' adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. , 2009, Genes & development.

[14]  R. Sunkar,et al.  Novel and Stress-Regulated MicroRNAs and Other Small RNAs from Arabidopsis , 2004, The Plant Cell Online.

[15]  Mahboob Ul Hussain.  Micro-RNAs (miRNAs): genomic organisation, biogenesis and mode of action. , 2012, Cell and tissue research.

[16]  Xuemei Chen,et al.  microRNA biogenesis and function in plants , 2005, FEBS letters.

[17]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[18]  Yijun Qi,et al.  Biochemical specialization within Arabidopsis RNA silencing pathways. , 2005, Molecular cell.

[19]  G. Meister,et al.  Regulation of microRNA biogenesis and function , 2012, Thrombosis and Haemostasis.

[20]  J. Steitz,et al.  Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR , 2007, Proceedings of the National Academy of Sciences.

[21]  O. Voinnet.  Origin, Biogenesis, and Activity of Plant MicroRNAs , 2009, Cell.

[22]  B. Moss,et al.  5'-Terminal and internal methylated nucleotide sequences in HeLa cell mRNA. , 1976, Biochemistry.

[23]  Z. Szweykowska-Kulinska,et al.  The crosstalk between plant microRNA biogenesis factors and the spliceosome , 2013, Plant signaling & behavior.

[24]  C. Timpte,et al.  Induction of sporulation in Saccharomyces cerevisiae leads to the formation of N6-methyladenosine in mRNA: a potential mechanism for the activity of the IME4 gene. , 2002, Nucleic acids research.

[25]  S. Luo,et al.  Global identification of microRNA–target RNA pairs by parallel analysis of RNA ends , 2008, Nature Biotechnology.

[26]  B. Davidson,et al.  RNA polymerase III transcribes human microRNAs , 2006, Nature Structural &Molecular Biology.

[27]  T. Pan.  N6-methyl-adenosine modification in messenger and long non-coding RNA. , 2013, Trends in biochemical sciences.

[28]  U. Schibler,et al.  Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells. , 1977, Journal of molecular biology.

[29]  Saeed Tavazoie,et al.  HNRNPA2B1 Is a Mediator of m6A-Dependent Nuclear RNA Processing Events , 2015, Cell.

[30]  J. Bokar.  The biosynthesis and functional roles of methylated nucleosides in eukaryotic mRNA , 2005 .

[31]  S. Tavazoie,et al.  N6-methyladenosine marks primary microRNAs for processing , 2015, Nature.

[32]  O. Elemento,et al.  Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons , 2012, Cell.

[33]  Yuda Fang,et al.  Identification of Nuclear Dicing Bodies Containing Proteins for MicroRNA Biogenesis in Living Arabidopsis Plants , 2007, Current Biology.

[34]  Yukio Kawahara,et al.  RNA editing of the microRNA‐151 precursor blocks cleavage by the Dicer–TRBP complex , 2007, EMBO reports.

[35]  A. Pasquinelli,et al.  Regulation by let-7 and lin-4 miRNAs Results in Target mRNA Degradation , 2005, Cell.

[36]  Artur Jarmolowski,et al.  Developmentally regulated expression and complex processing of barley pri-microRNAs , 2012, BMC Genomics.

[37]  Yuasa Takashi,et al.  The interaction between DCL1 and HYL1 is important for efficient and precise processing of pri-miRNA in plant microRNA biogenesis. , 2005, RNA.

[38]  Arne Klungland,et al.  ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. , 2013, Molecular cell.

[39]  Hajime Sakai,et al.  Regulation of Flowering Time and Floral Organ Identity by a MicroRNA and Its APETALA2-Like Target Genes Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.016238. , 2003, The Plant Cell Online.

[40]  Donald Grierson,et al.  Yeast targets for mRNA methylation , 2010, Nucleic acids research.

[41]  V. Chiang,et al.  Adenylation of plant miRNAs , 2009, Nucleic acids research.

[42]  G. Hannon,et al.  Processing of primary microRNAs by the Microprocessor complex , 2004, Nature.

[43]  F. Rottman,et al.  Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. , 1994, The Journal of biological chemistry.

[44]  S. Zhong,et al.  Adenosine Methylation in Arabidopsis mRNA is Associated with the 3′ End and Reduced Levels Cause Developmental Defects , 2012, Front. Plant Sci..

[45]  Gang Wu,et al.  Nuclear processing and export of microRNAs in Arabidopsis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[46]  V. Kim.  MicroRNA biogenesis: coordinated cropping and dicing , 2005, Nature Reviews Molecular Cell Biology.

[47]  V. Kim,et al.  Regulation of microRNA biogenesis , 2014, Nature Reviews Molecular Cell Biology.

[48]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[49]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[50]  Michel Herzog,et al.  MTA Is an Arabidopsis Messenger RNA Adenosine Methylase and Interacts with a Homolog of a Sex-Specific Splicing Factor[W][OA] , 2008, The Plant Cell Online.

[51]  F. Rottman,et al.  Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. , 1997, RNA.

[52]  Xuemei Chen,et al.  Methylation as a Crucial Step in Plant microRNA Biogenesis , 2005, Science.

[53]  W. Filipowicz,et al.  Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. , 2009, Current opinion in cell biology.

[54]  Xuemei Chen,et al.  Uridylation of miRNAs by HEN1 SUPPRESSOR1 in Arabidopsis , 2012, Current Biology.

[55]  C. Joo,et al.  Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. , 2008, Molecular cell.

[56]  E. Lai,et al.  Vive la différence: biogenesis and evolution of microRNAs in plants and animals , 2011, Genome Biology.

[57]  E. Sontheimer,et al.  Origins and Mechanisms of miRNAs and siRNAs , 2009, Cell.

[58]  Franck Vazquez,et al.  The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development. , 2004, Genes & development.

[59]  Gunnar Rätsch,et al.  Dual roles of the nuclear cap-binding complex and SERRATE in pre-mRNA splicing and microRNA processing in Arabidopsis thaliana , 2008, Proceedings of the National Academy of Sciences.

[60]  P. Meltzer.  Cancer genomics: Small RNAs with big impacts , 2005, Nature.

[61]  W. Filipowicz,et al.  The widespread regulation of microRNA biogenesis, function and decay , 2010, Nature Reviews Genetics.

[62]  F. Pagani,et al.  Cross talk between spliceosome and microprocessor defines the fate of pre‐mRNA , 2014, Wiley interdisciplinary reviews. RNA.

[63]  P. Seeburg,et al.  Modulation of microRNA processing and expression through RNA editing by ADAR deaminases , 2006, Nature Structural &Molecular Biology.

[64]  W. Filipowicz,et al.  Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? , 2008, Nature Reviews Genetics.

[65]  E. Izaurralde,et al.  Gene silencing by microRNAs: contributions of translational repression and mRNA decay , 2011, Nature Reviews Genetics.

[66]  R. Schwab,et al.  Enhanced microRNA accumulation through stemloop‐adjacent introns , 2013, EMBO reports.

[67]  Yvonne Tay,et al.  MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation , 2008, Nature.

[68]  B. Moss,et al.  Degradation of host microRNAs by poxvirus poly(A) polymerase reveals terminal RNA methylation as a protective antiviral mechanism. , 2012, Cell host & microbe.

[69]  W. Karłowski,et al.  The liverwort Pellia endiviifolia shares microtranscriptomic traits that are common to green algae and land plants , 2014, The New phytologist.

[70]  N. Shomron,et al.  Interplay between pre-mRNA splicing and microRNA biogenesis within the supraspliceosome , 2014, Nucleic acids research.

[71]  A. Hatzigeorgiou,et al.  Redirection of Silencing Targets by Adenosine-to-Inosine Editing of miRNAs , 2007, Science.

[72]  R. Gregory,et al.  Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in embryonic stem cells , 2009, Nature Structural &Molecular Biology.

[73]  Xuemei Chen,et al.  Methylation Protects miRNAs and siRNAs from a 3′-End Uridylation Activity in Arabidopsis , 2005, Current Biology.

[74]  V. Kim,et al.  The nuclear RNase III Drosha initiates microRNA processing , 2003, Nature.

[75]  Sven Rahmann,et al.  N6-Adenosine Methylation in MiRNAs , 2015, PloS one.

[76]  A. Barta,et al.  Introns of plant pri-miRNAs enhance miRNA biogenesis , 2013, EMBO reports.

[77]  V. Kim,et al.  Biogenesis of small RNAs in animals , 2009, Nature Reviews Molecular Cell Biology.

[78]  B. Cullen,et al.  Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. , 2003, Genes & development.

[79]  H. Vaucheret,et al.  The Nuclear dsRNA Binding Protein HYL1 Is Required for MicroRNA Accumulation and Plant Development, but Not Posttranscriptional Transgene Silencing , 2004, Current Biology.

[80]  R. Gregory,et al.  Many roads to maturity: microRNA biogenesis pathways and their regulation , 2009, Nature Cell Biology.

[81]  Chengqi Yi,et al.  N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO , 2011, Nature chemical biology.

[82]  B. Cullen,et al.  MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[83]  Zhike Lu,et al.  Unique Features of the m6A Methylome in Arabidopsis thaliana , 2014, Nature Communications.