Biology Reference
In-Depth Information
mRNA degradation are miRNA- and target-specific, remains to be
clarified.
As mentioned above, the function of piRNAs in silencing repeat
elements may be directly coupled with their biogenesis. Whether they
may also play a role in transcriptional gene silencing (TGS) remains to be
further investigated. In flies, Aub and Piwi mutants with low levels of
rasiRNAs
85
have been shown to lose the histone 3 lysine 9 methylation
and HP1 protein binding that normally are the mark of silenced chro-
matin loci.
56
In mouse, knockouts of Mili and Miwi-2 show DNA
demethylation at the retrotransposon loci concomitant with transposon
expression.
60,86
These studies support the potential function of Piwi
proteins and piRNAs in TGS mechanisms.
6. MicroRNA Gene Prediction
6.1. What Does a miRNA Precursor Look Like?
The discovery of the first miRNA that is strongly conserved in animals,
let-7,
1,2
prompted computational biologists to design methods for
genome-wide prediction of miRNA genes. The spectrum of RNA mole-
cules that are processed by Drosha and Dicer is still unclear, but a
few features that appear to be important for processing have been
discovered and incorporated in various combinations in miRNA gene
prediction tools.
6.1.1. Stable hairpin precursors
The study of Lee
et al
.
6
indicated that mature miRNAs are processed
from stem-loop precursor structures; and for 3868 of the 4115 animal
miRNAs that are present in the 10.1 release of the miRNA Registry
(http://microrna.sanger.ac.uk/sequences/), one can indeed predict a
simple stem-loop as the minimal free energy structure. Stem-loops are,
however, very frequently predicted in whole genomes. For instance,
Lim
et al
.
81
predicted secondary structures in regions of the human
genome that were conserved in mouse. Selecting stem-loops with at least
25 base pairs and with a free energy of folding of at least 25 kcal/mol
