The inner nuclear membrane protein Lem2 coordinates RNA degradation at the nuclear periphery

Journal Nat. Struct. Mol. Biol. 29, 910–921 (2022)
Title The inner nuclear membrane protein Lem2 coordinates RNA degradation at the nuclear periphery
Laboratory Nuclear Dynamics Group〈SA Prof. HIRAOKA Yasushi〉

Transcriptionally silent chromatin often localizes to the nuclear periphery. However, whether the nuclear envelope (NE) is a site for post-transcriptional gene repression is not well understood. Here we demonstrate that Schizosaccharomyces pombe Lem2, an NE protein, regulates nuclear-exosome-mediated RNA degradation. Lem2 deletion causes accumulation of RNA precursors and meiotic transcripts and de-localization of an engineered exosome substrate from the nuclear periphery. Lem2 does not directly bind RNA but instead interacts with the exosome-targeting MTREC complex and its human homolog PAXT to promote RNA recruitment. This pathway acts largely independently of nuclear bodies where exosome factors assemble. Nutrient availability modulates Lem2 regulation of meiotic transcripts, implying that this pathway is environmentally responsive. Our work reveals that multiple spatially distinct degradation pathways exist. Among these, Lem2 coordinates RNA surveillance of meiotic transcripts and non-coding RNAs by recruiting exosome co-factors to the nuclear periphery.


Lucía Martín Caballero (1, 2), Matías Capella (1, 3), Ramón Ramos Barrales (1, 4), Nikolay Dobrev (5, 6), Thomas van Emden (1, 2), Yasuhiro Hirano (7), Vishnu N Suma Sreechakram (1, 8), Sabine Fischer-Burkart (1), Yasuha Kinugasa (7, 9), Alicia Nevers (10, 11), Mathieu Rougemaille (10), Irmgard Sinning (5), Tamás Fischer (5, 12), Yasushi Hiraoka (7), Sigurd Braun (1, 2, 8)

  1. BioMedical Center (BMC), Division of Physiological Chemistry, Faculty of Medicine, LMU Munich, Planegg-Martinsried, Germany.
  2. International Max Planck Research School for Molecular and Cellular Life Sciences, Planegg-Martinsried, Germany.
  3. Instituto de Agrobiotecnología del Litoral, CONICET, Universidad Nacional del Litoral, Santa Fe, Argentina.
  4. Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-Consejo Superior de Investigaciones Científicas-Junta de Andalucía, Seville, Spain.
  5. Heidelberg University Biochemistry Center (BZH), Heidelberg, Germany.
  6. European Molecular Biology Laboratory, Hamburg Unit, Hamburg, Germany.
  7. Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
  8. Institute for Genetics, Justus-Liebig-University Giessen, Giessen, Germany.
  9. Regulation for intractable Infectious Diseases, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
  10. Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.
  11. University Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France.
  12. The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
PubMed 36123402