Understanding how cells keep gene transcription precisely in check is fundamental to maintaining genome integrity and ensuring normal development. Mammalian genomes contain hundreds of thousands of enhancers and promoters—regulatory elements that can initiate transcription by RNA Polymerase II in both directions. If not properly controlled, this widespread (“pervasive”) transcription produces large amounts of extragenic RNAs that may disrupt nuclear organization, cause DNA damage, and interfere with normal gene regulation.
Dr. Gioacchino Natoli's lab has recently identified Restrictor, a conserved and essential protein complex found across animals (metazoans), which patrols thousands of non-coding transcription units and halts RNA Polymerase II activity through a still-unknown mechanism. Unlike previously known termination systems, Restrictor operates without enzymatic cleavage, acting as a unique “off-switch” for transcription. This discovery opens new avenues for understanding how cells distinguish between productive gene transcription and potentially harmful background transcriptional noise.
This project, funded by the Italian Ministry of University and Research (MUR) under the Fondo Italiano per la Scienza (FIS2 Call) aims to contribute to understanding the mechanisms involved in Restrictor-mediated termination and its impact on genome integrity.
Posted on October 13, 2025