Poster abstracts
Poster number 94 submitted by Ava Barnes
Translational Regulation of NRXN1
Ava Barnes (Carnegie Mellon University, Department of Biological Sciences ), Gemma May (Carnegie Mellon University, Department of Biological Sciences ), Lucia Johnson (Carnegie Mellon University, Department of Biological Sciences ), Dr. Joel Mcmanus (Carnegie Mellon University, Department of Biological Sciences )
Abstract:
Neurexins are essential presynaptic adhesion molecules implicated in numerous neurodevelopmental disorders. The NRXN1 gene is one of the strongest genetic risk factors for autism and schizophrenia. NRXN1 has multiple promoters that drive transcription of mRNA isoforms with alternative 5' UTRs that encode different proteoforms. Although much is known about NRXN1, the specific role of promoter controlled 5’UTRs in translation regulation is largely unexplored. These 5’UTRs differ in length and predicted RNA structure, suggesting differences in ribosome recruitment and translation initiation. We investigated how alternative NRXN1 5’ UTRs influence its translation, comparing translation from the p1 promoter derived longer 5’UTR, p2 and p9 derived mid length 5’UTRs, and the p12 promoter derived shorter 5’UTR utilizing matching reporter constructs in a human neuroblast cell line. We also quantified the effect of upstream open reading frames and RNA structure within these 5’UTRs. We found both the 5’UTRs and RNA structures to be repressive of translation. These findings provide insight into NRXN1 gene expression, with implications for synaptic functions and the mechanisms underlying neurodevelopmental disorders.
References:
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Keywords: NRXN 1 , Translational Regulation