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typically results in only one of the 5
arms of the hairpin being incor-
porated into the Argonaute protein. This asymmetry appears to be
imposed through another structural constraint, namely that the pairing
of the 5
or 3
end of the miRNA within the miRNA-miRNA* duplex is less
stable than the pairing at the 5
end of the miRNA*.
6.1.3. Position-dependent selection strength
The pattern of evolutionary conservation along the miRNA precursor
was one of the first features to be incorporated in miRNA prediction
methods. Lai et al . 92 studied the alignments of 24 orthologous pre-
miRNAs in D. melanogaster and D. pseudoobscura and found that the
mature form exhibits the maximum degree of conservation, followed by
the complementary strand and then by the loop sequence, which shows
the mimumum amount of conservation. Only precursors obeying this
order in the number of mutations observed between D. melanogaster
and D. pseudoobscura were considered as candidate miRNA precursors.
Numerous other studies used this feature for miRNA gene prediction.
Berezikov et al . 95 made the additional requirement that the putative
miRNA precursor is flanked by regions of even lower conservation than
the loop to predict miRNAs that are conserved between primates and
rodents.
6.1.4. Sequence composition
There is little evidence of sequence specificity in miRNA processing, and
miRNA precursors are not especially G/C-poor or G/C-rich. Mature
miRNAs tend, however, to start with a U nucleotide. Of the 619 human
mature miRNA forms present in miRBase, 235 (38%) start with U, even
though the U content of these miRNAs is only 28%.
6.1.5. miRNA gene prediction methods
Many methods for miRNA gene prediction have been proposed, but they
can be categorized based on a relatively small number of parameters.
First, there are methods that aim to predict miRNA genes based solely
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