The inner nuclear membrane protein Lem2 coordinates RNA degradation at the nuclear periphery.
The inner nuclear membrane protein Lem2 coordinates RNA degradation at the nuclear periphery.
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DOI：
10.1038/s41594-022-00831-6
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发表时间：
2022-09
影响因子：
16.8
通讯作者：
Braun, Sigurd
中科院分区：
文献类型：
--
作者：
Caballero, Lucia Martin;Capella, Matias;Barrales, Ramon Ramos;Dobrev, Nikolay;van Emden, Thomas;Hirano, Yasuhiro;Sreechakram, Vishnu N. Suma;Fischer-Burkart, Sabine;Kinugasa, Yasuha;Nevers, Alicia;Rougemaille, Mathieu;Sinning, Irmgard;Fischer, Tamas;Hiraoka, Yasushi;Braun, Sigurd
转录沉默的染色质通常定位于核周边。然而，核被膜（NE）是否是转录后基因抑制的位点还不清楚。在这里，我们证明了裂殖酵母Lem 2，NE蛋白，调节核外泌体介导的RNA降解。Lem 2缺失导致RNA前体和减数分裂转录物的积累以及工程化外泌体底物从核周边的去定位。Lem 2不直接结合RNA，而是与靶向外泌体的MTREC复合物及其人同源物PAXT相互作用以促进RNA募集。该途径在很大程度上独立于外泌体因子组装的核体发挥作用。营养供应调节Lem 2调节减数分裂成绩单，这意味着这条途径是环境响应。我们的工作表明，存在多个空间上不同的降解途径。其中，Lem 2通过将外来体辅因子募集到核周边来协调减数分裂转录本和非编码RNA的RNA监视。Braun实验室表明，保守的核膜蛋白Lem 2与核-外泌体途径的MTREC复合物相互作用，以促进裂殖酵母核周边ncRNA和减数分裂转录物的募集和降解。
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. The Braun lab shows that the conserved nuclear membrane protein Lem2 interacts with the MTREC complex of the nuclear-exosome pathway to promote recruitment and degradation of ncRNAs and meiotic transcripts at the nuclear periphery in Schizosaccharomyces pombe.
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DOI：
10.1261/rna.044479.114
发表时间：
2014-06
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Egan ED;Braun CR;Gygi SP;Moazed D
通讯作者：
Moazed D
影响因子：
3.3
作者：
Graham, AC;Kiss, DL;Andrulis, ED
通讯作者：
Andrulis, ED
影响因子：
4.8
作者：
Caputo, Sandrine;Couprie, Joel;Zinn-Justin, Sophie
通讯作者：
Zinn-Justin, Sophie
影响因子：
3.7
作者：
Bitton, Danny A.;Schubert, Falk;Baehler, Jureg
通讯作者：
Baehler, Jureg
影响因子：
64.5
作者：
Braun S;Garcia JF;Rowley M;Rougemaille M;Shankar S;Madhani HD
通讯作者：
Madhani HD