Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Center for RNA Systems Biology (CRSB), University of California, Berkeley, Berkeley, United States; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, United States
Department of Biology, Howard Hughes Medical Institute, Brandeis University, Waltham, United States; National Center for Behavior Genomics, Brandeis University, Waltham, United States
Department of Biology, Howard Hughes Medical Institute, Brandeis University, Waltham, United States; National Center for Behavior Genomics, Brandeis University, Waltham, United States
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Center for RNA Systems Biology (CRSB), University of California, Berkeley, Berkeley, United States; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, United States
Although alternative pre-mRNA splicing (AS) significantly diversifies the neuronal proteome, the extent of AS is still unknown due in part to the large number of diverse cell types in the brain. To address this complexity issue, we used an annotation-free computational method to analyze and compare the AS profiles between small specific groups of Drosophila circadian neurons. The method, the Junction Usage Model (JUM), allows the comprehensive profiling of both known and novel AS events from specific RNA-seq libraries. The results show that many diverse and novel pre-mRNA isoforms are preferentially expressed in one class of clock neuron and also absent from the more standard Drosophila head RNA preparation. These AS events are enriched in potassium channels important for neuronal firing, and there are also cycling isoforms with no detectable underlying transcriptional oscillations. The results suggest massive AS regulation in the brain that is also likely important for circadian regulation.
