Transcription shapes spatial organization of eukaryotic genes
Despite the well-established role of nuclear organization in the regulation of gene expression, little is known about the reverse: how transcription shapes the spatial organization of the genome. In particular, given the relatively small sizes of genes and the limited resolution of light microscopy, the structure and spatial arrangement of a single transcribed gene are poorly understood.
We made use of several long highly expressed mammalian genes and demonstrated that they form Transcription Loops with polymerases moving along the loops and carrying nascent RNAs that undergo co-transcriptional splicing. This finding rules out a popular hypothesis about eukaryotic transcription occurring in so called Transcription Factories with immobilized polymerases and genes reeling through them.
Transcription loops dynamically modify their harboring loci and extend into the nuclear interior suggesting an intrinsic stiffness of these structures. Both experimental evidence and polymer modeling support the hypothesis that transcription loop stiffness results from the dense decoration of transcribed genes with multiple voluminous nascent RNPs.
We propose that transcription loop formation is the universal principle of eukaryotic gene expression, which has not been appreciated until now due to the limitation of light microscopy resolution and due to the small size or low expression of studied genes.
Webinar + Auditorium, IGBMC
Dr Irina Solovei
Biocenter, Ludwig Maximilians University, Munich