Bioinformatický seminár

Tue 17 Feb. 2009, 17:20

Title: Stark et al. (2007) Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes
Speaker: Broňa Brejová

Budeme diskutovať o článku

Stark A, Kheradpour P, Parts L, Brennecke J, Hodges E, Hannon GJ, Kellis M.
Systematic discovery and characterization of fly microRNAs using 12
Drosophila genomes. Genome Res. 2007 Dec;17(12):1865-79. Epub 2007 Nov 7.

MicroRNAs (miRNAs) are short regulatory RNAs that inhibit target
genes by complementary binding in 3' untranslated regions (3'
UTRs). They are one of the most abundant classes of regulators,
targeting a large fraction of all genes, making their
comprehensive study a requirement for understanding regulation
and development. Here we use 12 Drosophila genomes to define
structural and evolutionary signatures of miRNA hairpins, which
we use for their de novo discovery. We predict >41 novel miRNA
genes, which encompass many unique families, and 28 of which are
validated experimentally. We also define signals for the precise
start position of mature miRNAs, which suggest corrections of
previously known miRNAs, often leading to drastic changes in
their predicted target spectrum. We show that miRNA discovery
power scales with the number and divergence of species compared,
suggesting that such approaches can be successful in human as
dozens of mammalian genomes become available. Interestingly, for
some miRNAs sense and anti-sense hairpins score highly and mature
miRNAs from both strands can indeed be found in vivo. Similarly,
miRNAs with weak 5' end predictions show increased in vivo
processing of multiple alternate 5' ends and have fewer predicted
targets. Lastly, we show that several miRNA star sequences score
highly and are likely functional. For mir-10 in particular, both
arms show abundant processing, and both show highly conserved
target sites in Hox genes, suggesting a possible cooperation of
the two arms, and their role as a master Hox regulator.