Noncoding RNAs: Silenced No More

Posted December 10, 2007
Presented By
Overview
The contribution of RNA to chromatin structure and gene regulation is coming to light, and roles for these molecules have been found in diverse processes including transcriptional regulation, chromosomal replication, chromatin structure, epigenetic inheritance, inactivation of the X chromosome in females, gene imprinting, and protein stability. To discuss the emerging knowledge of ncRNAs in transcriptional regulation and chromatin organization, researchers gathered at the New York Academy of Sciences on October 17, 2007.
Elissa Lei discussed results indicating that noncoding RNAs appear to play an important role in the formation of chromatin insulators, which establish a scaffold upon which DNA can be transcribed. Emily Bernstein presented work showing that silencing of the genes on the inactive X chromosome (Xi) in females involves RNA molecules as well as other factors that regulate the association of histone-binding proteins. Darryl Conte's work suggested that small noncoding RNAs may play a role in the formation of heterochromatin and participate in gene silencing throughout the entire genome. Alexander Mazo presented evidence that gene expression within the first few hours of embryonic development in Drosophila appears to be controlled by noncoding RNAs that themselves are regulated by epigenetic regulators.
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Web Sites
The noncoding RNA database
The noncoding RNA (ncRNA) database provides information on the sequences and functions of transcripts which do not code for proteins, but perform regulatory roles in the cell.
RNAdb
A comprehensive mammalian noncoding RNA database (RNAdb) containing sequences and annotations for tens of thousands of noncoding RNAs.
Wikipedia entry on noncoding RNA
A basic resource with links to other articles.
Wormbook: the online review of C. elegans biology
A description of the over 1300 genes that produce functional noncoding RNA (ncRNA) transcripts in C. elegans.
Books
Barciszewski J, Erdmann VA, eds. 2003. Noncoding RNAs: Molecular Biology and Molecular Medicine. Landes Bioscience/Springer-Verlag, New York.
Galun, E. 2005. RNA Silencing. World Scientific Publishing Company, Singapore.
Allis CD, Jenuwein T, Reinberg D, Caparros M-L. 2007. Epigenetics. Cold Spring Harbor Laboratory Press, New York.
Publications
Emily Bernstein
Bernstein E, Allis CD. 2005. RNA meets chromatin. Genes Dev. 19: 1635-1655. Full Text
Bernstein E, Duncan EM, Masui O, et al. 2006. Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin. Mol. Cell. Biol. 26: 2560-2569. Full Text
Bernstein E, Kim SY, Carmell MA, et al. 2003. Dicer is essential for mouse development. Nat. Genet. 35: 215-217.
Goldberg AD, Allis CD, Bernstein E. 2007. Epigenetics: a landscape takes shape. Cell 128: 635-638.
Darryl Conte
Duchaine TF, Wohlschlegel JA, Kennedy S, et al. 2006. Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in multiple small-RNA-mediated pathways. Cell 124: 343-354.
Grishok A, Pasquinelli AE, Conte D, et al. 2001. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106: 23-34.
Mello CC, Conte D Jr. 2004. Revealing the world of RNA interference. Nature 431: 338-342.
Wang D, Kennedy S, Conte D, et al. 2005. Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants. Nature 436: 593-597.
Elissa Lei
Caretti G, Lei EP, Sartorelli V. 2007. The DEAD-box p68/p72 proteins and the noncoding RNA steroid receptor activator SRA: eclectic regulators of disparate biological functions. Cell Cycle 6: 1172-1176.
Lei EP, Corces VG. 2006. RNA interference machinery influences the nuclear organization of a chromatin insulator. Nat. Genet. 38: 936-941.
Lei EP, Corces VG. 2006. A long-distance relationship between RNAi and Polycomb. Cell 124: 886-888.
Alexander Mazo
Mazo A, Hodgson JW, Petruk S, et al. 2007. Transcriptional interference: an unexpected layer of complexity in gene regulation. J. Cell. Sci. 120(Pt 16): 2755-2761.
Petruk S, Sedkov Y, Brock HW, Mazo A. 2007. A model for initiation of mosaic HOX gene expression patterns by non-coding RNAs in early embryos. RNA Biol. 4: 1-6.
Petruk S, Sedkov Y, Riley KM, et al. 2006. Transcription of bxd noncoding RNAs promoted by trithorax represses Ubx in cis by transcriptional interference. Cell 127: 1209-1221. Full Text
Petruk S, Sedkov Y, Smith S, et al. 2001. Trithorax and dCBP acting in a complex to maintain expression of a homeotic gene. Science 294: 1331-1334.
General Background
Cousin J. 2002. Small RNAs make a big splash. Science 298: 2296-2297.
The ENCODE Project Consortium, 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature (in press).
Grishok A, Tabara H, Mello CC. 2000. Genetic requirements for inheritance of RNAi in C. elegans. Science 287: 2494-2497.
Mattick JS. 2005. The functional genomics of noncoding RNA. Science 309: 1527-1528.
Storz G. 2002. An expanding universe of noncoding RNAs. Science 296: 1260-1263.
Speakers
Emily Bernstein, PhD
The Rockefeller University
e-mail | web site | publications
Emily Bernstein is a postdoctoral associate in the laboratory of David Allis at the Rockefeller University. She will be starting her own research group in the new year at Mount Sinai School of Medicine, Department of Oncological Sciences.
Darryl Conte, PhD
University of Massachusetts Medical Center
e-mail | web site | publications
Darryl Conte is a research assistant professor in the laboratory of Craig Mello at the University of Massachusetts Medical Center. He did his graduate work at the Wadsworth Center and SUNY Albany.
Elissa Lei, PhD
National Institute of Diabetes and Digestive and Kidney Diseases
e-mail | web site | publications
Elissa Lei obtained her PhD in 2003 for her work on mRNA nuclear export in the laboratory of Pamela Silver at Harvard Medical School. Her postdoctoral research on RNA silencing and chromatin organization was carried out in the laboratory of Victor Corces at Johns Hopkins University. She established her independent research group in 2006 in the Laboratory of Cellular and Developmental Biology at the National Institute of Diabetes and Digestive and Kidney Diseases.
Alexander M. Mazo, PhD
Thomas Jefferson University
e-mail | web site | publications
Alexander Mazo is a professor in the Department of Biochemistry and Molecular Biology and Kimmel Cancer Center at Thomas Jefferson University.
Catherine Zandonella
Catherine Zandonella is a science writer based in New York City, covering such topics as environmental science, public health, and applied technology. She has a master's degree in public health from the University of California, Berkeley. Zandonella has written for a number of publications, including New Scientist, The Scientist, and Nature.