Gene loops enhance mRNA export in yeast (560.8)

Abstract

Extraordinary progress has been made in recent years toward understanding the structure of the eukaryotic genome and the mechanisms that underlie gene expression. Missing from the picture, though, is a fundamental understanding of the three‐dimensional organization of the genome and how these structures affect gene expression. We are investigating the higher order structure of genes transcribed by RNA polymerase II (RNAP II) in the yeast Saccharomyces cerevisiae. Using a powerful technique, called “chromosome conformation capture”, designed to probe the three‐dimensional architecture of the genome, we have detected gene loops that specifically juxtapose promoter and terminator regions. Gene loops are formed on actively transcribed genes and are dependent upon components of both the initiation and pre‐mRNA 3’‐end processing machineries. However, neither the structural requirements for formation and maintenance of gene loops, nor the functions of gene loops are well understood. Here, we report that gene loops are RNA‐dependent and facilitate export of mRNA from the nucleus to the cytoplasm. Further, our systematic analysis of genetic and physical requirements for looping (1) Define the transcription and mRNA export factors TREX‐1 and TREX‐2 as required for formation and/or maintenance of gene loops; (2) Determine the function of gene loops by defining how gene loops, the nuclear pore and mRNA export are interconnected. Our working hypothesis is that all protein‐encoding genes form loops. Looping is not essential, but rather facilitates mRNA export by interaction with nuclear pore complex. This is consistent with (i) coupling of export to transcription of nascent mRNA and (ii) interaction of actively transcribed genes to the nuclear pore. Our results define a fundamental process involved in gene expression and illuminate the pathway by which transcription is coupled to mRNA export.Grant Funding Source: Supported by NIH