Can RNA-processing hotspots serve as post-transcriptional enhancers?
Together with the David Horn lab (University of Dundee), we observed that in trypanosomes the single expressed antigen coding gene displays a specific inter-chromosomal interaction with a major mRNA splicing locus. Chromosome conformation capture (Hi-C) revealed a dynamic reconfiguration of this inter-chromosomal interaction upon activation of another antigen. Using super-resolution microscopy we were able to show the interaction to be heritable and splicing dependent.
Our results reveal a novel mechanism to ensure monogenic expression, requiring the spatial integration of antigen transcription and mRNA splicing in a dedicated compartment. These findings suggest a new means of post-transcriptional gene regulation.
Faria J#, Luzak V#, Mueller LSM#, Brink BG, Hutchinson S, Glover L, Horn D*, and Siegel TN* (2020)
Antigenic variation by switching inter-chromosomal interactions with an RNA splicing locus in trypanosomes.
bioRxiv 2020.01.27.921452 doi.org/10.1101/2020.01.27.921452
# equal contribution
* corresponding authors
members of the Siegel lab are listed in bold