EVANSTON, Ill. --- Researchers at Northwestern University and CarnegieMellon University have found that a recently described class ofmolecules called microRNAs (miRNAs) play an important role inregulating oogenesis, the process by which females make eggs. MiRNAssilence genes by binding to genetic elements called messenger RNA andpreventing them from making new proteins -- the molecules primarilyresponsible for cell activities.
While previous research has identified some miRNA targets,investigators haven't yet seen how they impact developmental processes.
"We found the first evidence that miRNAs are involved in oogenesis, andthis adds an extra layer of complexity that needs to be explored if weare to understand how development is regulated," said Jonathan Minden,associate professor of biological sciences at Carnegie Mellon and oneof the paper's authors.
The findings will be published online the week of Aug. 8 by the Proceedings of the National Academy of Sciences (PNAS).
"If miRNAs are missing from a developing egg, then it fails to developto term, and the net result is infertility," said lead author RichardW. Carthew, Owen L. Coon Professor of Molecular Biology atNorthwestern. "It is intriguing to think that miRNA dysfunction mightbe at the root cause of certain forms of infertility. We already knowthat miRNAs are involved in cancer and stem cell biology."
Investigators were initially surprised to find that miRNAsaffected only a small fraction of expressed genes within a maturingegg. On closer inspection, they found that the genes affected by miRNAsshared common roles as regulators of protein manufacturing or turnover.These results suggest that miRNAs tightly control the abundance ofproteins throughout the process of oogenesis and fertilization.
Using a proteomics tool developed at Carnegie Mellon, the scientistscompared maturing fruit fly eggs. One group of eggs was missing a geneessential for producing miRNAs, whereas another group of eggs hadnormal miRNA production. (All plants and animals have DICER, the genethe produces miRNAs, so the researchers used a "genetic trick" togenerate DICER-less eggs.)
In comparing overall protein production between these two groups, theresearchers discovered that miRNAs stopped the manufacturing of a smallgroup of key proteins, including ones that produce ribosomes. Thesestructures constitute the cell's protein-making machinery, and theirshutdown would render cells unable to produce new proteins.
The investigators also found that miRNAs appear to attenuate proteinturnover. They speculate that this function may allow a developing eggto accumulate large amounts of specific proteins necessary to drive theamazing structural changes seen in embryogenesis.
In addition to Carthew and Minden, other authors on the PNAS paper areKenji Nakahara and Kevin Kim of Northwestern University and ChristinSciulli and Susan Dowd of Carnegie Mellon University.
The research was supported by the National Institutes of Health.
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