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MicroRNAs are very short RNAs that may regulate gene expression.
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Animal and plant genomes code for many short (~22 base) RNA molecules, called microRNAs.
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MicroRNAs regulate gene expression by base pairing with complementary sequences in target mRNAs.
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Figure 11.39
lin4 RNA regulates expression of lin14 by binding to the 3′ nontranslated region.
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Very small RNAs are gene regulators in many eukaryotes.
The first example was discovered in the nematode C. elegans
as the result of the interaction between the regulator gene lin4
and its target gene, lin14. Figure 11.39
illustrates the behavior of this regulatory system. The lin14 target
gene regulates larval development. Expression of lin14 is controlled by
lin4, which codes for a small transcript of 22 nucleotides (2195;
2196). The lin4 transcripts are complementary to a 10 base sequence
that is repeated 7 times in the 3′ nontranslated region of lin14.
Expression of lin4 represses expression of lin14
posttranscriptionally, most likely because the base pairing reaction
between the two RNAs leads to degradation of the mRNA. This system is
especially interesting in implicating the 3′ end as a site for
regulation.
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The lin4 RNA is an example of a microRNA (miRNA).
There are ~80 genes in the C. elegans genome coding
for microRNAs of 21-24 nucleotide length (2193; 2194).
They have varying patterns of expression during development and are
likely to be regulators of gene expression. Many of the microRNAs of C. elegans
are contained in a large (15S) ribonucleoprotein particle (2510).
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>Many of the C. elegans microRNAs have homologues in mammals,
so the mechanism may be widespread. They are also found in plants.
Of 16 microRNAs in Arabidopsis, 8 are completely conserved in rice,
suggesting widespread conservation of this regulatory mechanism (3027).
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The mechanism of production of the microRNAs is also widely
conserved. In the example of lin4,
the gene is transcribed into a transcript that forms a double-stranded
region that becomes a target for a nuclease called Dicer. This has an
N-terminal helicase activity, enabling it to unwind the double-stranded
region, and two nuclease domains that are related to the bacterial
ribonuclease III. Related enzymes are found in flies, worms, and plants
(3028; 3029; 3027). Cleavage of the initial
transcript generates the active microRNA. Interfering with the enzyme
activity blocks the production of microRNAs and causes developmental
defects.
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Another step in the formation of
microRNAs has been characterized in plants, where the 3′ terminal
nucleotide is methylated on its ribose by the methyltransferase enzyme
HEN1. The methylation stabilizes the microRNA (5837) .
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Last Revised on March 3, 2005
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2193 Lau, N. C., Lim, l. e. E. P., Weinstein, E. G., and Bartel, d. a. V. P.
(2001).
An abundant class of tiny RNAs with probable regulatory roles in C. elegans.
Science 294, 858-862.
PubMed Journal
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2194 Lee, R. C. and Ambros, V.
(2001).
An extensive class of small RNAs in C. eleganss.
Science 294, 862-864.
PubMed Journal
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2195 Lee, R. C., Feinbaum, R. L., and Ambros, V.
(1993).
The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
Cell 75, 843-854.
PubMed Journal
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2196 Wightman, B., Ha, I., and Ruvkun, G.
(1993).
Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.
Cell 75, 855-862.
PubMed Journal
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2510 Mourelatos, Z., Dostie, J., Paushkin, S., Sharma, A., Charroux, B., Abel, L., Rappsilber, J., Mann, M., and Dreyfuss, G.
(2002).
miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs.
Genes Dev. 16, 720-728.
PubMed Journal
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3027 Reinhart, B. J., Weinstein, E. G., Rhoades, M. W., Bartel, B., and Bartel, D. P.
(2002).
MicroRNAs in plants.
Genes Dev. 16, 1616-1626.
PubMed Journal
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3028 Bernstein, E., Caudy, A. A., Hammond, S. M., and Hannon, G. J.
(2001).
Role for a bidentate ribonuclease in the initiation step of RNA interference.
Nature 409, 363-366.
PubMed Journal
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3029 Ketting, R. F., Fischer, S. E., Bernstein, E., Sijen, T., Hannon, G. J., and Plasterk, R. H.
(2001).
Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans.
Genes Dev. 15, 2654-2659.
PubMed Journal
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5837 Yu, B., Yang, Z., Li, J., Minakhina, S., Yang, M., Padgett, R. W., Steward, R., and Chen, X.
(2005).
Methylation as a crucial step in plant microRNA biogenesis.
Science 307, 932-935.
PubMed
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© Jones and Bartlett Publishers (2007)
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