BioMedical Center (BMC), Division of Physiological Chemistry, Faculty of Medicine, LMU Munich, Planegg-Martinsried, Germany.
International Max Planck Research School for Molecular and Cellular Life Sciences, Planegg-Martinsried, Germany.
Nat Struct Mol Biol. 2022 Sep;29(9):910-921. doi: 10.1038/s41594-022-00831-6. Epub 2022 Sep 19.
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.
转录沉默的染色质通常定位于核周。然而,核膜(NE)是否是转录后基因沉默的位点尚不清楚。在这里,我们证明裂殖酵母 Lem2,一种 NE 蛋白,调节核小体介导的 RNA 降解。Lem2 缺失导致 RNA 前体和减数分裂转录物的积累,以及工程化的核小体底物从核周向化。Lem2 不直接结合 RNA,而是与核小体靶向 MTREC 复合物及其人类同源物 PAXT 相互作用,以促进 RNA 的募集。该途径主要独立于核体,核体是核小体因子组装的地方。营养物质的可用性调节 Lem2 对减数分裂转录物的调节,这意味着该途径对环境有响应。我们的工作揭示了多种空间上不同的降解途径的存在。在这些途径中,Lem2 通过将核小体共因子募集到核周,协调减数分裂转录物和非编码 RNA 的 RNA 监测。