Breaking news from the indomitable vinegar fly about animals’ lust for size.
A KAIST-KRIBB biological research collaboration has recently led to the discovery of a novel mechanism modulating animal growth control. Growth control is a fascinating process to study because it determines how large an animal is allowed to get – as we know, some animals are enormous and some are miniscule in size. A research effort headed by Jones’ Lab for Behavioral Neurobiology at KAIST screened a library of genetically modified fly strains created in that lab; these strains permitted the over-expression of miRNAs in specific fly tissues. The findings were extended to mammalian cell lines. While the insulin-producing cells of flies and mammals have different anatomical locations and embryonic origins, it was found to be that human miR-9 also down-regulates the human sNPFR homologue NPY2R.
How does an animal know how large it should be? Why aren’t there humans the size of elephants or elephants the size of ants? A team led by Professor Walton Jones of the Department of Biological Sciences in the KAIST College of Life Science and Bio-Engineering, in collaboration with the lab of Dr. Kweon Yu of KRIBB, recently discovered new aspects of the mechanisms that control the regulation of animal growth.
Their noteworthy findings have been published in the well-known journal Nature Communications. Featured in this work, two graduate students Shreelatha Bhat and Yoon-Seok Suh, screened a library of genetically modified fly strains created in the Jones lab that permit the over-expression of miRNAs in specific fly tissues. MicroRNAs are short, single-stranded RNA molecules that act in the context of a protein complex to down-regulate target messenger RNAs. In the screen described in this paper, ~150 miRNAs were over-expressed in the insulin-producing cells (IPCs), which are known to regulate growth. This screen eventually led the team to narrow their focus to the study of miR-9a because its over-expression strongly reduces tissue growth. In addition to this ability, miR-9a is also endogenously expressed in the IPCs where it induces degradation of mRNAs encoding a neuropeptide receptor called sNPFR. Since previous experiments had already shown that sNPFR regulates insulin production, these experiments have established a causative link between the expression of the highly conserved miR-9a and insulin signaling.
The Jones and Yu labs have extended these findings to mammalian cell lines where human miR-9 also down-regulates the human sNPFR homologue NPY2R. This is somewhat surprising given that the insulin-producing cells of flies and mammals have different anatomical locations and embryonic origins. Future experiments will address whether the relationship between miR-9, NPY2R, and insulin extend to mammalian development and growth control.
Professor Jones was happy to note, “This is yet another example of the indomitable vinegar fly informing our understanding of ‘so-called’ higher organisms.”
Suh YS et al. (2015) Genome-wide microRNA screening reveals that the evolutionary conserved miR-9a regulates body growth by targeting sNPFR1/NPYR. Nat. Comms. 6:7693
* lab webpage