Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation

Denis Torre, Yesai S. Fstkchyan, Jessica Sook Yuin Ho, Youngseo Cheon, Roosheel S. Patel, Emma J. Degrace, Slim Mzoughi, Megan Schwarz, Kevin Mohammed, Ji Seon Seo, Raquel Romero-Bueno, Deniz Demircioglu, Dan Hasson, Weijing Tang, Sameehan U. Mahajani, Laura Campisi, Simin Zheng, Won Suk Song, Ying chih Wang, Hardik ShahNancy Francoeur, Juan Soto, Zelda Salfati, Matthew T. Weirauch, Peter Warburton, Kristin Beaumont, Melissa L. Smith, Lubbertus Mulder, S. Armando Villalta, Kai Kessenbrock, Cholsoon Jang, Daeyoup Lee, Silvia De Rubeis, Inma Cobos, Oliver Tam, Molly Gale Hammell, Marcus Seldin, Yongsheng Shi, Uttiya Basu, Vittorio Sebastiano, Minji Byun, Robert Sebra, Brad R. Rosenberg, Chris Benner, Ernesto Guccione, Ivan Marazzi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Endogenous retroviruses (ERVs) are remnants of ancient parasitic infections and comprise sizable portions of most genomes. Although epigenetic mechanisms silence most ERVs by generating a repressive environment that prevents their expression (heterochromatin), little is known about mechanisms silencing ERVs residing in open regions of the genome (euchromatin). This is particularly important during embryonic development, where induction and repression of distinct classes of ERVs occur in short temporal windows. Here, we demonstrate that transcription-associated RNA degradation by the nuclear RNA exosome and Integrator is a regulatory mechanism that controls the productive transcription of most genes and many ERVs involved in preimplantation development. Disrupting nuclear RNA catabolism promotes dedifferentiation to a totipotent-like state characterized by defects in RNAPII elongation and decreased expression of long genes (gene-length asymmetry). Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards RNAPII activity, ERV expression, cell identity, and developmental potency.

Original languageEnglish
Pages (from-to)4255-4271.e9
JournalMolecular cell
Issue number23
StatePublished - Dec 7 2023


  • 2CLC
  • Integrator
  • RNA catabolism
  • elongation
  • endogenous retrovirus
  • non-coding RNA
  • stem cell
  • totipotent-like cells
  • transcription-associated RNA degradation


Dive into the research topics of 'Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation'. Together they form a unique fingerprint.

Cite this