Striking circadian neuron diversity and cycling of Drosophila alternative splicing

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Abstract

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

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Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE77451).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77451

Article and author information

Author details

Qingqing Wang

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Katharine C Abruzzi

Department of Biology, National Center of Behavioral Genomics, Howard Hughes Medical Institute, Brandeis University, Waltham, United States

For correspondence
katea@brandeis.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3949-3095
Michael Rosbash

Department of Biology, National Center of Behavioral Genomics, Howard Hughes Medical Institute, Brandeis University, Waltham, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3366-1780
Donald C Rio

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

For correspondence
don_rio@berkeley.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4775-3515

Funding

Arnold and Mabel Beckman Foundation (Postdoctoral Fellowship)

Qingqing Wang

Howard Hughes Medical Institute

Michael Rosbash

National Institutes of Health (R01GM097352)

Donald C Rio

National Institutes of Health (R35GM118121)

Donald C Rio

National Institutes of Health (NIH P50102706)

Donald C Rio

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.