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Transcriptome-wide Analysis of Alternative Splicing in Primates During Neuronal Development

  • Author(s): Ronaghi, Neda
  • Advisor(s): Sanford, Jeremy
  • et al.
Abstract

Alternative splicing (AS) is a major mechanism of post-transcriptional gene regulation that contributes to transcriptome diversity in mammals. Alternatively spliced events are a hallmark of neuronal differentiation and it has been revealed that AS events in the brain are more highly conserved in comparison to other tissues. The advent of powerful RNA-seq technologies has transformed our ability to profile AS on a transcriptome-wide scale, and in this project we carried out an evolutionary comparison of changes in the mRNA processing of Homo sapiens and Rhesus macaque. We leveraged RNA-seq to study in vitro neuronal differentiation over the course of 5 weeks in human and rhesus. Upon mapping the RNAseq data, we assembled the RNA-seq alignments into potential transcripts. We further identified, quantified, and tested different types of alternative splicing events, and focused on skipped exon events that were differentially spliced between different time points. We next narrowed down our analysis to orthologous skipped exon events to identify temporally regulated species-specific and conserved alternative splicing patterns. Together, our data reveal mRNA isoforms that are biologically relevant during the early stages of neuronal differentiation.

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