Functional characterization of the several splice variants of Fmr1

Fmr1 has been known to be a crucial contributor in neurodevelopment. Events such as alternative splicing in its coding region and the use of different trancription start and end sites in its non-coding regions result in the production of a range of mRNA transcripts. Structural and functional characterization of some of these transcripts have been performed, but several of them remain uncharacterized. Differences in the temporal and spatial expession of these transcripts may play important roles in regulating the development of the fetal and adult brain structures and thus, their physiological functions.

The extensive set of experiments suggested in this study plan exploit mice brain, neuronal cultures and in vitro studies. The proposed study for the identification and full characterization of the known and novel transcripts of Fmr1 is an important initial step towards the assignment of the specific known roles and the determination of the so-far unknown roles of Fmr1 at the various stages of neurodevelopment. This systematic study helps in categorizing the transcripts that can produce stable proteins and further understand their cellular localization and cellular functions individually and in concert with each other. Similarly, identification of the non-coding transcripts helps us in exploring their roles in the regulatory processes, if any, which might also impact the expression of the coding transcripts in the neuronal cells.