eBriefing

The Global View of miRNA: Strategies for Visualizing miRNA Expression

The Global View of miRNA
Reported by
Eva Derman

Posted February 07, 2007

Overview

MicroRNAs (miRNAs), a class of small RNA molecules that are 21–23 nucleotides in length, are the newest addition to the repertoire of regulatory factors that control gene expression. The distinguishing feature of miRNAs is that they arise from precursor molecules that are 70-100 nucleotides long with a characteristic stem-loop structure. Unlike polypeptide transcriptional factors, miRNAs are not active in the nucleus, but are active in the cytoplasm where they regulate gene expression after transcription.

On October 3, 2006 the RNAi Discussion Group held a meeting focused on ways to identify and determine the function of miRNAs. Topics discussed included computational and direct cloning approaches for cataloging miRNAs, several methods for verifying the expression of candidate miRNAs, and efforts to identify miRNAs involved in specific developmental processes.

Use the tabs above to find a meeting report and multimedia from this event.

Web Sites

miRBase
This web site hosts a comprehensive and searchable database of published miRNA sequences.

Gene Tools
GeneTools is the sole supplier of research quantities of morpholinos. The web site provides information about the applications of morpholinos in miRNA research.

454 Life Sciences
454 Life Sciences provides services and instrumentation for high-throughput deep DNA sequencing.


Journal Articles

Overview

Baskerville S, Bartel DP. 2005. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11: 241-247.

Johnston RJ, Hobert O. 2003. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 2003. 426: 845-849.

Kloosterman WP, Plasterk RH. 2006. The diverse functions of microRNAs in animal development and disease. Dev. Cell 11: 441-450.

Leaman D, Chen PY, Fak J, et al. 2005. Antisense-mediated depletion reveals essential and specific functions of microRNAs in Drosophila development. Cell 121: 1097-1108.

Lee Y, Kim M, Han J, et al. 2004. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 23: 4051-4060. Full Text

Lewis BP, Shih IH, Jones-Rhoades MW, et al. 2003. Prediction of mammalian microRNA targets. Cell 115: 787-798.

Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. 2005. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat. Cell Biol. 7: 719-723.

Pei Y, Tuschl T. 2006. On the art of identifying effective and specific siRNAs. Nat. Methods 3: 670-676.

Pillai RS, Bhattacharyya SN, Artus CG, et al. 2005. Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309: 1573-1576.

Xie X, Lu J, Kulbokas EJ, et al. 2005. Systematic discovery of regulatory motifs in human promoters and 3′UTRs by comparison of several mammals. Nature 434: 338-345.

Xuezhong C, Hagedornm CT, Cullen BR. 2004. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10: 1957-1966. Full Text

Drosophila microRNAs: From Genes to Functions

Aboobaker AA, Tomancak P, Patel N, et al. 2005. Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development. Proc. Natl. Acad. Sci. USA. 102: 17-22. Full Text

Buescher M, Tio M, Tear G, et al. 2006. Functions of the segment polarity genes midline and H15 in Drosophila melanogaster neurogenesis. Dev. Biol. 292: 418-429.

Dubrovsky EB, Dubrovskaya VA, Levinger L, et al. 2004. Drosophila RNase Z processes mitochondrial and nuclear pre-tRNA 3′ ends in vivo. Nucleic Acids Res. 32: 255-262. Full Text

Lai EC. 2002. Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat. Genet. 4: 363-364.

Lai EC, Tomancak P, Williams RW, Rubin GM. 2003. Computational identification of Drosophila microRNA genes. Genome Biol. 4:R42. Full Text

Margulies M, Egholm M, Altman WE, et al. 2005. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437: 376-380. Full Text

Ng M, Diaz-Benjumea FJ, Vincent JP, et al. 1996. Specification of the wing by localized expression of wingless protein. Nature 381: 316-318.

MicroRNA Expression and Functional Analysis

Ason B, Darnell DK, Wittbrodt B, et al. 2006. Differences in vertebrate microRNA expression. Proc. Natl. Acad. Sci. USA. 103: 14385-14389.

Kloosterman WP, Wienholds E, de Bruijn E, et al. 2006. In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes. Nat. Methods 1: 27-29.

Kloosterman WP, Steiner FA, Berezikov E, et al. 2006. Cloning and expression of new microRNAs from zebrafish. Nucleic Acids Res. 34: 2558-2569. Full Text

Poy MN, Eliasson L, Krutzfeldt J, et al. 2004. A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432: 226-230.

Vester B, Wengel J. 2004. LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA. Biochemistry 43: 13233-132341.

Wienholds E, Kloosterman WP, Miska E, et al. 2005. MicroRNA expression in zebrafish embryonic development. Science 309: 310-311.

Cell-type and Tissue-specific miRNAs Determined by Small RNA Library Cloning

Alizadeh AA, Eisen MB, Davis RE, et al. 2000. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403: 503-511.

Altuvia Y, Landgraf P, Lithwick G, et al. 2005. Clustering and conservation patterns of human microRNAs. Nucleic Acids Res. 33: 2697-706. Full Text

Chen CZ, Li L, Lodish H, Bartel, DP. 2004. MicroRNAs modulate hematopoietic lineage differentiation. Science 303: 83-86.

Naguibneva I, Ameyar-Zazoua M, Polesskaya A, et al. 2006. The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat. Cell Biol. 8: 278-284.

Tools and Strategies to Analyze miRNAs

Kiriakidou M, Nelson PT, Kouranov A, et al. 2004. A combined computational-experimental approach predicts human microRNA targets. Genes Dev. 18: 1165-1178. Full Text

Nelson PT, Baldwin DA, Kloosterman WP, et al. 2006. RAKE and LNA-ISH reveal microRNA expression and localization in archival human brain. RNA 2: 187-191. Full Text

Nelson PT, Baldwin DA, Scearce LM, et al. 2004. Microarray-based, high-throughput gene expression profiling of microRNAs. Nat. Methods. 2: 155-161.

Nelson PT, Hatzigeorgiou AG, Mourelatos Z. 2004. miRNP:mRNA association in polyribosomes in a human neuronal cell line. RNA 3: 387-394. Full Text

Speakers

Eric Lai, PhD

Memorial Sloan-Kettering Cancer Center
e-mail | web site | publications

Eric Lai is an assistant member of the Department of Developmental Biology at Memorial Sloan-Kettering Cancer Center and assistant professor in the program in Cell Biology and Genetics at Weill Cornell Medical School. He received his PhD in biology from the University of California, San Diego. He was a postdoctoral fellow at HHMI/Department of Molecular and Cell Biology in the laboratory of Gerald Rubin at the University of California, Berkeley. Lai received the Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund in 2005 and was a special fellow of the Leukemia and Lymphoma Society from 2004 to 2006.

Wigard Kloosterman

Netherlands Institute for Developmental Biology
e-mail | publications

Wigard Kloosterman studied biology and received a master in biotechnology at the University of Groningen, The Netherlands (1998–2003). In August 2003, he began his graduate studies in the lab of Ronald Plasterk at the Hubrecht Laboratory, Utrecht, The Netherlands, where he is studying microRNA expression and function in the zebrafish embryo.

Pablo Landgraf, MD, PhD

The Rockefeller University
e-mail | web site | publications

Pablo Landgraf is a postdoctoral fellow in the laboratory of Thomas Tuschl at the Rockefeller University. Landgraf received his MD from the Ludwig- Maximilians- University (LMU) of Munich in 2001. In 2003 he received his PhD from the Department of Clinical Biochemistry at Haunersches Children's Hospital, University of Munich. His thesis was titled "The identification of the peroxisomal targeting signal of the Adrenoleukodystrophy Protein partially conserved within the family of peroxisomal ABC-Transporters." Landgraf's current research is miRNA expression profiling in mammals.

Zissimos Mourelatos, MD

University of Pennsylvania School of Medicine
e-mail | web site | publications

Zissimos Mourelatos is assistant professor of pathology and laboratory medicine at the University of Pennsylvania School of Medicine. He studies the basic biology of small regulatory RNAs and how misregulation of RNA pathways contributes to motor neuron degeneration. Mourelatos has received the Michael S. Brown New Investigator Research Award for his work. His lab has developed novel technologies to profile miRNAs and to study their cellular and subcellular distribution in healthy and diseased human tissue. Mourelatos received his MD from the Aristotelian University of Thessaloniki (Greece) in 1991.


Eva Derman

Eva Derman is a molecular biologist and science writer based in New York City. For 20 years she was Head of Laboratory and Associate Member of the Department of Developmental and Structural Biology at the Public Health Research Institute, where she conducted research on gene structure and regulation, molecular immunology, molecular endocrinology, and other topics.