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

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.
Schemes in figures were created with BioRender.com. S. B. was supported by the German Research Foundation (DFG) through the collaborative research center CRC 1064 (project ID 213249687-SFB 1064) and the research grant BR 3511/4-1. I. S. was supported by the Leibniz program of the DFG (SI586/6-1). Additional support was provided by the Australian Government through the Australian Research Council’s Discovery Projects funding scheme awarded to T. F. (project DP190100423); by the Centre National pour la Recherche Scientifique and the Agence Nationale de la Recherche to M. R. (ANR-16-CE12-0031); and by the JSPS KAKENHI grants to Y. Hirano (JP19K06489, JP20H05891), Y. K. (JP19K23725), and Y. Hiraoka (JP18H05533, JP19K22389).