Functional relevance of miRNA sequences in human disease.

MicroRNA (miRNA) processing in the cytoplasm produces a miRNA duplex containing the forward, miRNA strand and the reverse, miRNA strand, which was thought to be degraded. However, recent evidence is challenging this dogma that miRNA is simply a non-functional byproduct of miRNA biogenesis. We present a comprehensive review of evidence that miRNA plays a significant role in cellular function and assembled a table outlining all of the publications before September 2011 that have reported on miRNA activity in human disease. Furthermore, we will present unexpected diagnostic and therapeutic implications due to the active miRNA status.

[1]  V. Ambros,et al.  An Extensive Class of Small RNAs in Caenorhabditis elegans , 2001, Science.

[2]  V. Kim,et al.  The Drosha-DGCR8 complex in primary microRNA processing. , 2004, Genes & development.

[3]  Nan Shen,et al.  miR-155 and its star-form partner miR-155* cooperatively regulate type I interferon production by human plasmacytoid dendritic cells. , 2010, Blood.

[4]  S. Barik,et al.  Ectopic expression of miR-126*, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cells , 2008, Journal of Molecular Medicine.

[5]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[6]  Brian S. Roberts,et al.  The colorectal microRNAome. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Haber,et al.  Dual Role for Argonautes in MicroRNA Processing and Posttranscriptional Regulation of MicroRNA Expression , 2007, Cell.

[8]  Malachi Griffith,et al.  In-depth characterization of the microRNA transcriptome in a leukemia progression model. , 2008, Genome research.

[9]  Phillip D. Zamore,et al.  Drosophila microRNAs Are Sorted into Functionally Distinct Argonaute Complexes after Production by Dicer-1 , 2007, Cell.

[10]  Mirko H. H. Schmidt,et al.  miR-126 and miR-126*: New Players in Cancer , 2010, TheScientificWorldJournal.

[11]  M. Serra,et al.  Comprehensive thermodynamic analysis of 3′ double-nucleotide overhangs neighboring Watson–Crick terminal base pairs , 2006, Nucleic acids research.

[12]  C. Croce,et al.  MicroRNAs in Cancer. , 2009, Annual review of medicine.

[13]  R. Shiekhattar,et al.  Human RISC Couples MicroRNA Biogenesis and Posttranscriptional Gene Silencing , 2005, Cell.

[14]  P. Zamore,et al.  ATP Requirements and Small Interfering RNA Structure in the RNA Interference Pathway , 2001, Cell.

[15]  K. Jażdżewski,et al.  Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer , 2009, Proceedings of the National Academy of Sciences.

[16]  Xiaodong Wang,et al.  Argonaute2 Cleaves the Anti-Guide Strand of siRNA during RISC Activation , 2005, Cell.

[17]  Henning Urlaub,et al.  Single-Stranded Antisense siRNAs Guide Target RNA Cleavage in RNAi , 2002, Cell.

[18]  Hiroyuki Yamamoto,et al.  A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. , 2010, Cancer cell.

[19]  David P. Bartel,et al.  Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals , 2008, Nature.

[20]  Phillip D. Zamore,et al.  Sorting of Drosophila Small Silencing RNAs , 2007, Cell.

[21]  P. Sharp,et al.  RNAi Double-Stranded RNA Directs the ATP-Dependent Cleavage of mRNA at 21 to 23 Nucleotide Intervals , 2000, Cell.

[22]  Jung-Eun Park,et al.  Altered microRNA regulation in Huntington's disease models , 2011, Experimental Neurology.

[23]  S. Jayasena,et al.  Functional siRNAs and miRNAs Exhibit Strand Bias , 2003, Cell.

[24]  B. Rollins,et al.  microRNA expression in the biology, prognosis, and therapy of Waldenström macroglobulinemia. , 2009, Blood.

[25]  Iris Barshack,et al.  MiR‐92b and miR‐9/9* Are Specifically Expressed in Brain Primary Tumors and Can Be Used to Differentiate Primary from Metastatic Brain Tumors , 2008, Brain pathology.

[26]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[27]  F. Sato,et al.  Polo‐like kinase 1 regulates cell proliferation and is targeted by miR‐593* in esophageal cancer , 2011, International journal of cancer.

[28]  T. Tuschl,et al.  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells , 2001, Nature.

[29]  Yi Xing,et al.  The Bifunctional microRNA miR-9/miR-9* Regulates REST and CoREST and Is Downregulated in Huntington's Disease , 2008, The Journal of Neuroscience.

[30]  P. Gunaratne,et al.  Discovery of Novel MicroRNAs in Female Reproductive Tract Using Next Generation Sequencing , 2010, PloS one.

[31]  Hervé Seitz,et al.  Argonaute Loading Improves the 5′ Precision of Both MicroRNAs and Their miRNA∗ Strands in Flies , 2008, Current Biology.

[32]  Ji Young Kim,et al.  MicroRNA miR-199a* Regulates the MET Proto-oncogene and the Downstream Extracellular Signal-regulated Kinase 2 (ERK2)* , 2008, Journal of Biological Chemistry.

[33]  Nicholas Bertos,et al.  miR-378(∗) mediates metabolic shift in breast cancer cells via the PGC-1β/ERRγ transcriptional pathway. , 2010, Cell metabolism.

[34]  M. Zavolan,et al.  Strand-specific 5'-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity. , 2007, RNA.

[35]  Z. Weng,et al.  Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. , 2010, RNA.

[36]  Ryan D. Morin,et al.  Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells. , 2011, Blood.

[37]  Jennifer A. Doudna,et al.  Structural insights into RNA Processing by the Human RISC-Loading Complex , 2009, Nature Structural &Molecular Biology.

[38]  J. Riethoven,et al.  miR-27b*, an oxidative stress-responsive microRNA modulates nuclear factor-kB pathway in RAW 264.7 cells , 2011, Molecular and Cellular Biochemistry.

[39]  T. Kwok,et al.  The miR-18a* microRNA functions as a potential tumor suppressor by targeting on K-Ras. , 2009, Carcinogenesis.

[40]  N. Rajewsky,et al.  A pancreatic islet-specific microRNA regulates insulin secretion , 2004, Nature.

[41]  T. Du,et al.  Asymmetry in the Assembly of the RNAi Enzyme Complex , 2003, Cell.

[42]  T. Tuschl,et al.  Identification of Novel Genes Coding for Small Expressed RNAs , 2001, Science.

[43]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[44]  E. Lai,et al.  Distinct mechanisms for microRNA strand selection by Drosophila Argonautes. , 2009, Molecular cell.

[45]  V. Ambros,et al.  The evolution of our thinking about microRNAs , 2008, Nature Medicine.

[46]  R. Aharonov,et al.  hsa-miR-29c* is linked to the prognosis of malignant pleural mesothelioma. , 2010, Cancer research.

[47]  Y. Tomari,et al.  Drosophila argonaute1 and argonaute2 employ distinct mechanisms for translational repression. , 2009, Molecular cell.

[48]  Wei Yan,et al.  Tissue-dependent paired expression of miRNAs , 2007, Nucleic acids research.

[49]  N. Hayward,et al.  Characterization of the Melanoma miRNAome by Deep Sequencing , 2010, PloS one.

[50]  Hong Duan,et al.  The regulatory activity of microRNA* species has substantial influence on microRNA and 3′ UTR evolution , 2008, Nature Structural &Molecular Biology.

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