SELECTION 2010
Short Title: Control of Argonaute-bound small-RNA stability in vivo
Coordinator: D. O’Carroll
Partner: A. Enright
miRNA expression is tightly controlled in space and time. Appropriate miRNA expression
is required for animal development and physiology. While a number of studies have
identified transcriptional regulators of miRNA expression, post-transcriptional control of
miRNA expression is a new and emerging area of research. We will focus on the
regulation of miRNA biogenesis and stability through RNA modifying enzymes. Our
starting point will be a class of poly(U) polymerase enzymes that have recently been
shown to modify miRNAs and their precursors in vitro. To this end we propose to explore
the function of controlled miRNA stability through the analysis of poly(U) polymerase Tut4
in the development and homeostasis of the miRNA-dependant hematopoietic system and
male germ cells.
This project will couple state-of-the-art mouse genetic strategies, high throughput
sequencing (HTS) and bioinformatic approaches. We will generate a conditional allele for
the Tut4 poly(U) polymerase in the mouse. Specific Cre alleles we be used to delete in
Tut4 in hematopoietic and germ cells. We propose to use HTS genomic approaches
(small-RNA seq, HTS-CLIP, RNA Seq) to relate the phenotype to a molecular mechanism.
Key to this endeavor is bioinformatic analysis and integration of large distinct genomic
data sets.
The successful candidate will join the O’Carroll lab at the EMBL Mouse Biology Unit in
Monterotondo, and interact frequently with the Enright group at EMBL-EBI. The post
holder will benefit from the mentorship of both group leaders to design investigative
approaches. This arrangement will provide an excellent opportunity for career
development, taking advantage of the resources and expertise of both EMBL laboratories
to execute this multidisciplinary project.
For more information see http://www.embl.it