MicroRNA or miRNA are small RNA molecules 21–23 nucleotides in length that can regulate (down-regulate) gene expression and are a recently identified molecular mechanism in embryonic development. This interaction of a small RNA molecule with target mRNAs is thought to regulate many aspects of the human transcriptome in the embryo and also in the adult. First identified in plants and in laval worm development and can also be called the RNA interference pathway.
microRNA Processing Steps
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Dicer is required for maintaining adult pancreas. Morita S, Hara A, Kojima I, Horii T, Kimura M, Kitamura T, Ochiya T, Nakanishi K, Matoba R, Matsubara K, Hatada I. PLoS ONE. 2009;4(1):e4212. Epub 2009 Jan 16.
This PNAS paper shows how a protein Dgrc8 (DiGeorge syndrome critical region gene 8) involved in microRNA processing affects skin development. Dgrc8 is an RNase III protein which has a key role in microRNA (miRNA) biogenesis.
DGCR8-dependent microRNA biogenesis is essential for skin development. Yi R, Pasolli HA, Landthaler M, Hafner M, Ojo T, Sheridan R, Sander C, O’Carroll D, Stoffel M, Tuschl T, Fuchs E. Proc Natl Acad Sci U S A. 2008 Dec 29.
"MicroRNAs play important roles in animal development. Numerous conditional knockout (cKO) studies of Dicer have been performed to interrogate the functions of microRNA during mammalian development. However, because Dicer was recently implicated in the biogenesis of endogenous siRNAs in mammals, it raises the question whether the Dicer cKO defects can be attributable to the loss of microRNAs. Previously, we and others conditionally targeted Dicer and identified its critical roles in embryonic skin morphogenesis. Here, we focus explicitly on microRNAs by taking a parallel strategy with Dgcr8, encoding an essential component of the microprocessor complex that is exclusively required for microRNA biogenesis. With this comparative analysis, we show definitively that the Dicer- and Dgcr8-null skin defects are both striking and indistinguishable. By deep sequencing analysis of microRNA depletion in both Dicer- and Dgcr8-null skin, we demonstrate that most abundantly expressed skin microRNAs are dependent on both Dicer and DGCR8. Our results underscore a specific importance of microRNAs in controlling mammalian skin development."
(More? Skin Development - Molecular Development - OMIM - Dgcr8)
Small RNA molecules 21–23 nucleotides in length bind to target messenger RNAs, this in turn down-regulate protein synthesis. This interaction of a small RNA molecule with target mRNAs is thought to regulate many aspects of the human transcriptome in both the developing embryo and in the adult. Initially identified in plants, then in worm development, the mechanism has now been described in many animals including humans.
Target mRNA binding has mainly been identified to the 3' untranslated regions (3' UTRs). MicroRNA target sequences can be either completely or significantly complementary to the mRNA.
Note that in plants some microRNAs also bind to coding sequences.
miRNA can be initially formed from a longer precursor miRNA (pre-miRNAs), processed and delivered to an RNA-induced silencing complex (RISC).
Dicer1 a component of the microRNA pathway and RNA interference.
Listed below are some sample microRNA molecules.
lin-4 - down-regulates LIN-14 protein in c. elegans (worm) larval development.
let-7
mir-14
mir-23
bantam
Reviews
MicroRNAs in embryonic stem cells. Wang Y, Keys DN, Au-Young JK, Chen C. J Cell Physiol. 2009 Feb;218(2):251-5. Review.
How do microRNAs regulate gene expression? Cannell IG, Kong YW, Bushell M. Biochem Soc Trans. 2008 Dec;36(Pt 6):1224-31. Review.
Articles
DGCR8-dependent microRNA biogenesis is essential for skin development. Yi R, Pasolli HA, Landthaler M, Hafner M, Ojo T, Sheridan R, Sander C, O’Carroll D, Stoffel M, Tuschl T, Fuchs E. Proc Natl Acad Sci U S A. 2008 Dec 29.
Dicer is required for maintaining adult pancreas. Morita S, Hara A, Kojima I, Horii T, Kimura M, Kitamura T, Ochiya T, Nakanishi K, Matoba R, Matsubara K, Hatada I. PLoS ONE. 2009;4(1):e4212. Epub 2009 Jan 16.
Dicer is essential for mouse development. Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, Mills AA, Elledge SJ, Anderson KV, Hannon GJ. Nat Genet. 2003 Nov;35(3):215-7. Epub 2003 Oct 5. Erratum in: Nat Genet. 2003 Nov;35(3):287.
Bookshelf
C. elegans II Riddle, Donald L.; Blumenthal, Thomas; Meyer, Barbara J.; Priess, James R., editors. Plainview (NY): Cold Spring Harbor Laboratory Press; c1997 lin-4 Down-regulates LIN-14 Protein | lin-14 mRNA and the lin-4 translational repressor.
Search PubMed: Search January 2008 "microRNA" 4,108 reference articles of which 935 were reviews. Search term = microRNA | Dicer | lin-4
Target Gene Prediction miRBase: the home of microRNA data
Target Gene Prediction microRNA.org
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MicroRNA interaction of a small RNA molecule with target mRNAs is thought to be evolutionarily ancient gene regulatory mechanism, which current research is finding regulates many aspects of the human transcriptome.
Please email Dr Mark Hill if you wish to make a comment about this current project.