The regulatory impact on neuronal survival of a small non-coding RNA molecule (iRNA) has been decoded at the highest resolution to date by an international team of researchers, led by Dr. Volker Busskamp from the Center for Regenerative Therapies Dresden at the TU Dresden (CRTD).

In order to protect patients from neurodegenerative diseases, the team of researchers seeks to decipher gene regulation to prime applications for strengthening neurons. The extensive methods used by this team to do it may become a new standard to study miRNAs.

While they were discovered more than 25 years ago, the impact of miRNAs on gene regulation of messenger RNAs (mRNAs) is still incomplete. Experimental studies usually provide only one or very few miRNA interactions; however computer-based studies predict maximum range of miRNA interactions that can even bind thousands of mRNAs.

In this study, the researchers found that brain-enriched miRNA (miR-124) is unnecessary during neuronal differentiation from adult human stem cells, but it has a huge effect on neuronal survival.

For the study, the multidisciplinary team of researchers performed an in-depth system level analysis of miR-124 by combining both experimental and computational approaches. The results showed that the 98 miR-124 targeted genes that are simultaneously regulated, many of which had physiological functions to protect neurons from dying. To also investigate the indirect effects (miR-124 targeted genes, which are regulators of gene expression), the research group used a novel computational approach.

Our deep mechanistic insights may lead to biomedical applications enabling the protection of neurons against degeneration. In addition, previously uncharacterised genes in the regulatory networks could be investigated and new functions assigned to them,” says Volker Busskamp. The interdisciplinary approach of experimental manipulation and sophisticated bioinformatic analysis sets new standards in the miRNA gene regulation research.


Source: Science Daily