Seeing through the developping lens:
deciphering the role of RNA binding proteins in PTGR
Chapter 1 Introduction
Through this project, we aim to decipher post-transcriptional regulation network in the developping lens.
In the past decades, post-transcriptional gene regulation (PTGR) was shown to be of particular importance in the developping lens. Indeed, the alteration of PTGR network can result in abnormal development of the lens, of the eye. For example, mutations in RNA binding proteins such as Celf1, Stau2, Tdrd7 has been associated to eye’s defects in animal models.
mutation in RNA binding protein Tdrd7 was associated with juvenile cataract in human and mice. Interestingly, this RNA binding protein interacts with crystallin transcript Crybb3. Lachke et al. (2011)
alteration of Stau2’s expression was associated with abnormal eye size through regulation of Sox2 and HES-1. Cockburn et al. (2012)
Celf1 is involved in fiber cell differenciation, required for nuclear degradation through its interactions with Dnase2b, p21^Cip1^ and p27^Kip1^. As much interesting, Celf1 controls splicing abundance of beta-spectrin and high transcripts levels of alpha-actinin 2 involved morphology of fiber cell. Siddam et al. (2018)
So as to accomplish our goal, we will highlight genes that seems to be ptx regulated in the lens. Our first approach will be to identify genes that exhibits same level of transcripts in epithelium and fiber cells but different levels of proteins. (Chapter 2)
Lachke, Salil A, Fowzan S Alkuraya, Stephen C Kneeland, Takbum Ohn, Anton Aboukhalil, Gareth R Howell, Irfan Saadi, et al. 2011. “Mutations in the RNA Granule Component TDRD7 Cause Cataract and Glaucoma” 331 (March): 1571–7.
Cockburn, Diane M, Jason Charish, Nardos G Tassew, James Eubanks, Rod Bremner, Paolo Macchi, and Philippe P Monnier. 2012. “The double-stranded RNA-binding protein Staufen 2 regulates eye size.” Molecular and Cellular Neuroscience 51 (3-4). Elsevier Inc.: 101–11. https://doi.org/10.1016/j.mcn.2012.08.008.
Siddam, Archana D, Carole Gautier-courteille, Linette Perez-campos, Justine Viet, Jeffrey M Gross, Luc Paillard, and Salil A Lachke. 2018. “The RNA-binding protein Celf1 post- transcriptionally regulates p27 Kip1 and Dnase2b to control fiber cell nuclear degradation in lens development,” 1–28.