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Nature Structural & Molecular BiologyMolecular BiologyPeer-reviewed journal article

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

Lucía Martín CaballeroiD, Matías CapellaiD, Ramón Ramos BarralesiD, Nikolay DobreviD, Thomas van EmdeniD, Yasuhiro HiranoiD, Vishnu N. Suma SreechakramiD, Sabine Fischer‐Burkart, Yasuha KinugasaiD, Alicia NeversiD, Mathieu RougemailleiD, Irmgard SinningiD, Tamás FischeriD, Yasushi HiraokaiD, Sigurd J BrauniD

PDFDOIPreprint

Abstract

Transcriptionally silent chromatin often localizes to the nuclear periphery. However, whether the nuclear envelope (NE) is a site for post-transcriptional gene repression is unknown. Here we demonstrate that S. pombe Lem2, an NE protein, regulates nuclear exosome-mediated RNA degradation. Lem2 deletion causes accumulation of non-coding RNAs and meiotic transcripts. Indeed, an engineered exosome substrate RNA shows Lem2-dependent localization to the nuclear periphery. Lem2 does not directly bind RNA, but instead physically interacts with the exosome-targeting MTREC complex and promotes RNA recruitment. The Lem2-assisted pathway acts independently of nuclear bodies where exosome factors assemble, revealing that multiple spatially distinct degradation pathways exist. The Lem2 pathway is environmentally responsive: nutrient availability modulates Lem2 regulation of meiotic transcripts. Our data indicate that Lem2 recruits exosome co-factors to the nuclear periphery to coordinate RNA surveillance and regulates transcripts during the mitosis-to-meiosis switch.

Citations
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