Lin & Ying 2006
Methods Mol Biol. 2006;342:295-312.
Gene silencing in vitro and in vivo using intronic microRNAs.
Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
small single-stranded regulatory RNAs capable of interfering with intracellular messenger RNAs (mRNAs)
that contain either complete or partial complementarity,
are useful for the design of new therapies
against cancer polymorphism and viral mutation.
I think they will find eventually that these MicroRNAs govern genetic memory – which is what I think epigenetics really is.
Numerous miRNAs have been reported to induce RNA interference (RNAi), a posttranscriptional gene-silencing mechanism. Recent evidence also indicates that
they are involved in the transcriptional regulation
of genome activities.
They were first discovered in Caenorhabditis elegans as native RNA fragments that modulate a wide range of genetic regulatory pathways during embryonic development, and are now recognized as small gene silencers transcribed from the noncoding regions of a genome.
In humans, nearly 97% of the genome is noncoding DNA,
which varies from one individual to another,
and changes in these sequences are frequently noted
to manifest clinical and circumstantial malfunction.
Type 2 myotonic dystrophy and fragile X syndrome were found to be associated with miRNAs derived from introns.
is a new class of miRNAs derived from the processing
of nonproteincoding regions of gene transcripts.
The intronic miRNAs differ uniquely from previously described intergenic miRNAs in the requirement of RNA polymerase (Pol)-II and spliceosomal components for its biogenesis. Several kinds of intronic miRNAs have been identified in C. elegans, mouse, and human cells; however, neither function nor application has been reported.
Here, we show for the first time that intron-derived miRNA is not only able to induce RNA interference (RNAi) in mammalian cells but also in fish, chicken embryos, and adult mice,
demonstrating the evolutionary preservation
of this gene regulation system in vivo.
These miRNA-mediated animal models provide artificial means to reproduce the mechanisms of miRNA-induced disease in vivo and will shed further light on miRNA-related therapies.
We are getting pretty small here folks – but of essential importance
Ying SY, Chang DC, Lin SL.
Mol Biotechnol. 2008 Mar;38(3):257-68. Epub 2007 Nov 13. Review.
PMID: 17999201 [PubMed – indexed for MEDLINE]
Lin SL, Chang DC, Ying SY.
Methods Mol Biol. 2006;342:313-20. Review.
PMID: 16957385 [PubMed – indexed for MEDLINE]
Lin SL, Ying SY.
Methods Mol Biol. 2006;342:295-312. Review.
PMID: 16957384 [PubMed – indexed for MEDLINE]
Ying SY, Chang DC, Miller JD, Lin SL.
Methods Mol Biol. 2006;342:1-18. Review.
PMID: 16957363 [PubMed – indexed for MEDLINE]
Lin SL, Chang D, Ying SY.
Gene. 2005 Aug 15;356:32-8.
PMID: 16005165 [PubMed – indexed for MEDLINE]
Grassmann & Jeang 2008
Biochim Biophys Acta. 2008 Nov;1779(11):706-11. Epub 2008 May 15.
The roles of microRNAs in mammalian virus infection.
Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany.
are post-transcriptional regulators of gene expression that are important for the control of a multitude of critical processes in mammalian cells.
Increasing evidence supports that miRNAs also have important functions in viral replication and may be used by host cells to control viral infection. Expression of miRNAs has been reported for various groups of viruses including herpesviruses, small DNA viruses and retroviruses. The recent identification of target genes regulated by some of these viral miRNAs suggests that they may function in the
control of lytic and latent viral replication, in the
limitation of antiviral responses, in the
inhibition of apoptosis, and in the
stimulation of cellular growth.
In this review, we summarize in brief recent findings on the
antiviral activities of cellular miRNAs and the
viral counter-responses to the cell’s RNAi restriction.
Miniature game of chess?
Kim et al 2008
Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16230-5. Epub 2008 Oct 13.
MicroRNA-directed transcriptional gene silencing in mammalian cells.
Graduate School of Biological Sciences and Division of Molecular Biology, Beckman Research Institute of the City of Hope, 1450 E. Duarte Road, Duarte, CA 91010, USA.
MicroRNAs (miRNAs) regulate gene expression at the posttranscriptional level in the cytoplasm [cytoplasm general term that applies to all the material found in the interior of a living cell, excluding the nucleus], but recent findings suggest additional roles for miRNAs in the nucleus.
To address whether miRNAs might transcriptionally silence gene expression, we searched for miRNA target sites proximal to known gene transcription start sites in the human genome.
One conserved miRNA, miR-320, is encoded within the promoter region of the cell cycle gene POLR3D in the antisense orientation. We provide evidence of a cis-regulatory role for miR-320 in
transcriptional silencing of POLR3D
[protein coding gene – temperature sensitive – Preferred Names polymerase (RNA) III (DNA directed) polypeptide D]
expression. miR-320 directs the association of RNA interference (RNAi) protein Argonaute-1 (AGO1), Polycomb group (PcG) component EZH2, and tri-methyl histone H3 lysine 27 (H3K27me3) with the POLR3D promoter.
Our results suggest the existence of an
of miRNA-directed transcriptional gene silencing (TGS) in mammalian cells.
Of course I don’t understand what this means, but interesting that from the first word I read of this abstract I had the clear “sense” that this is about epigenetics – and I almost felt a shock go through me when I read down to the word epigenetic.
Sullivan & Ganem 2005
Mol Cell. 2005 Oct 7;20(1):3-7.
MicroRNAs and viral infection.
Howard Hughes Medical Institute, Department of Microbiology, University of California, San Francisco, CA 94143, USA.
MicroRNAs (miRNAs) play a pivotal role in the regulation of genes
involved in diverse processes such as
development, differentiation, and cellular growth control.
Recently, many viral-encoded miRNAs have been discovered, for the most part in viruses transcribed from double-stranded DNA genomes. As with their cellular counterparts, the functions of most viral-derived miRNAs are unknown; however, functions have been documented or proposed for viral miRNAs from three different viral families-herpesviruses, polyomaviruses, and retroviruses. Several virus-encoded miRNAs have unique aspects to their biogenesis, such as the polymerase that transcribes them or their location within the precursor transcript. Additionally, viral interactions with cellular miRNAs have also been identified, and these have substantially expanded our appreciation of miRNA functions.