The dynamics of gene expression, from the nucleus to mitochondria

In this talk I will discuss our ongoing efforts to investigate gene regulatory processes occurring throughout the cell, from the nucleus to the mitochondria. We established native elongating transcript sequencing (NET-seq) and nanopore analysis of co-transcriptional processing (nano-COP) that probe transcription elongation and co-transcriptional processing. These approaches monitor where, when and how splicing occurs across long human nascent transcripts that contain multiple introns. Intriguingly, we found that proximal introns are more often spliced together than introns spaced apart, indicating that splicing of proximal introns is coordinated.

We are also interested in a fundamental question in eukaryotic gene expression: how are nuclear- and mitochondrial-encoded genes co-regulated? We have many projects to uncover how the mitochondrial genome is regulated, from DNA structure to translational control. Here I will discuss our latest work investigating how the mitochondrial genome is structured, which has revealed striking differences between mitochondrial and nuclear genome organization.