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MicroRNA works with Ago2 protein to regulate blood cell development

MicroRNAs became the stars of the RNA universe when, in 2001, scientists found that these short RNAs can control whether or not genes are expressed. This month, scientists at Rockefeller University and the Wellcome Trust cast new light on the genesis of these key biological regulators and how they carry out their function. These provocative new findings were reported online July 12 in the journal Genes & Development.

While microRNAs are made in large amounts in every cell from plants to humans, Dnal OCarroll, a research associate in Alexander Tarakhovskys lab at The Rockefeller University, has focused on understanding how they regulate the development of one particular system: the hematopoietic system.

This is a system where similar kinds of stem cells give rise to all the different types of blood cells in the body, so you can definitively address whether microRNAs are involved in the processes by which they specialize and develop, says OCarroll.

Instead of making proteins, these snippets of RNA repress their synthesis. They bind to messenger RNAs (mRNAs) the blueprints for proteins and either target them for destruction or inhibit their protein-making output. In order for microRNA to find its target mRNA, it needs the help of the protein Ago2, the only member of the Argonaute family of proteins that has a slicer function: That is, once microRNA binds with its target, it cleaves it, effectively stopping mRNAs ability to make proteins.

Since the slicer activity of Ago2 would be the most efficient way of regulating microRNA function, OCarroll wanted to see whether it plays a role in the development of blood cells.

In the bone marrow of adult mice where their blood stem cells reside OCarroll conditionally knocked out the gene that encodes Ago2. Two months later, OCarroll observed that they had developed anemia and enlarged spleens, and noted that although the stem cells still gave rise to all blood cell types, th
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Contact: Joseph Bonner
bonnerj@rockefeller.edu
212-327-8998
Rockefeller University
26-Jul-2007


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