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Determining fundamental cis-regulatory elements directing selective, efficient, and novel RNA editing


Adenosine Deaminase Acting on RNA (ADAR), modifies double-stranded RNA molecules through post-transcriptional hydrolytic deamination of specific adenosines, turning them into inosines (A-to-I RNA editing), which the ribosomal machinery detects as guanosine. These modifications often result in an amino acid change with profound consequences in protein function. Synaptotagmin 1 is a calcium sensor protein of the nervous system that has a pivotal role in the synapses for calcium dependent fast and synchronous neurotransmitter release. Intronic elements directing RNA secondary structures identified in the Syt 1 locus have been shown to direct editing in vitro. Here, through precise genetic engineering of syt 1 locus, we show a complex system of RNA editing in vivo. Each editing site consists of an adenosine with a specific level of editing across stages of development and tissues, controlled by an autonomous element. Simple modifications of these elements could have a big effect on editing level of a specific site. Here, we have shown that by modifying an element, editing could be completely abolished in a site; and by mimicking an element of a mosquito, editing levels would mimic that of mosquito\u2019s respective editing site as well; and also a completely new editing site can appear through modification of an element. We further show that mutations that cause modifications in the dsRNA secondary structure of syt 1, can not only modulate the editing efficiency of a specific site, but can also abolish editing at another site. This work offers evidence into the evolutionary development of how RNA editing sites appeared over the course of adaptive evolution. Further works could focus on implications of these changes in editing sites through behavioral analyses and electrophysiology and also further manipulation of editing in order to develop a desired phenotype.


Rezaei, Ali, and Fuchs, Michael, "Determining fundamental cis-regulatory elements directing selective, efficient, and novel RNA editing" (2015). Summer Research Symposium. Brown Digital Repository. Brown University Library.



  • Summer Research Symposium

    Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …