CHAMP RNA HELICASE · Function, Mechanism, and Regulation of Mammalian Mov10L1 RNA Helicase
FP7 — People (Marie Curie Actions)
- Duration
- 2012-04-01 → 2016-03-31
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-CIG
Lines connect the coordinator with its partners.
Results in brief
Function, Mechanism, and Regulation of Mammalian Mov10L1 RNA Helicase
The goal of this research is to decipher the molecular mechanism of mammalian putative RNA helicase MOV10L1 and its isoform MOV10L1-core (CHAMP), unwinding reaction and its structure-function relationship. How specific and nonspecific RNA substrates activate CHAMP, as a molecular motor, will reveal its role in RNA remodeling and therefore its function in RNA metabolism in the cell. In turn, this will reveal how MOV10L1 may regulate genes essential for the heart development during prenatal and postnatal stages. Currently this project has enabled us to develop state of the art tools and to pave the way to a new research field with very wide perspective. The impact this will have has on the lab future is very strong as our focus will now be mainly on these human RNA helicases. Therefore, this grant has really been in my opinion a breakthrough to achieve such independency and to grow into something with strong funding and publication potential. The work and conclusions that emerges from this project will provide the basis for a major project in this field. This funding has substantially impacted the future direction of future research. Furthermore, it is now because of the bench mark we have reached, we are now expanding this project into a much greater extent and two new PhD students are being hired. As the principle investigator of this project, this enable the well integration within the faculty and hosting institute. Moreover, specifically this integration grant has enable be to formulate a strong basis for my research group. Furthermore, during the course of the grant award a PhD student has completed his training directly linked to this project. The manuscript which is a results of her PhD is now under review. We have presented the outcome of this research work on several scientific meetings very successfully.
Data: CORDIS, © European Union
Project objective
Adult cardiac myocytes retain the ability to respond to a variety of stimuli by hypertrophic growth. Hypertrophy is initially beneficial, permitting enhanced cardiac output; it can ultimately become deleterious and result in cardiomyopathy, heart failure, and sudden death. Mitogenic signaling drives cell cycle progression as consequences of their effects on cyclins, which interact with cyclin-dependent kinases and cyclin-dependent kinase inhibitors. Recent work showed that CHAMP has antihypertrophic activity, which requires the conserved ATPase motif that is characteristic of RNA helicase superfamilies 1 and 2, and is associated with up-regulation of the cell cycle inhibitor p21CIP1 and p27KIP1. CHAMP is localized in the cytoplasm of cardiomyocytes and is likely regulates its target RNA at the level of translation and degradation. The regulation p21CIP1 and p27KIP1 translation levels controls the proliferation of cardiomyocytes by inhibiting cell cycle progression. However, very little is known regarding the molecular mechanism of how RNA helicases regulate translation. To date detailed enzymology regarding the mechanical transduction of RNA helicases is scarcely known, especially from superfamily 1 to which CHAMP is identified with. This proposal is aim to decipher the molecular mechanism of a putative RNA helicase CHAMP and how it regulates mRNA metabolism of genes essential for the heart development during prenatal stages and regulates CDKI’s mRNA in postnatal stages. The research program will integrate state of the art molecular biochemistry and biophysics approach with medicinal translational research. An interdisciplinary structured based team will be assembled to integrate knowledge, and capacity from molecular to physiological aspects of cardio myocytes hypertrophy. This will result from integration of key enzymatic regulators as CHAMP to the physiological regulation of cardiomyocytes hypertrophy response in human at the molecular level of mRNA metabolism.
Original text from CORDIS.
Participants
- TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY · HaifaCoordinatorIsrael
Links
Data: CORDIS, © European Union