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RNA 质量控制因子促使 Clr4/SUV39H 形成并引发组成型异染色质组装。

RNA quality control factors nucleate Clr4/SUV39H and trigger constitutive heterochromatin assembly.

机构信息

Massachusetts General Hospital Krantz Family Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.

Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Cell. 2024 Jun 20;187(13):3262-3283.e23. doi: 10.1016/j.cell.2024.04.042. Epub 2024 May 29.

DOI:10.1016/j.cell.2024.04.042
PMID:38815580
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11227895/
Abstract

In eukaryotes, the Suv39 family of proteins tri-methylate lysine 9 of histone H3 (H3K9me) to form constitutive heterochromatin. However, how Suv39 proteins are nucleated at heterochromatin is not fully described. In the fission yeast, current models posit that Argonaute1-associated small RNAs (sRNAs) nucleate the sole H3K9 methyltransferase, Clr4/SUV39H, to centromeres. Here, we show that in the absence of all sRNAs and H3K9me, the Mtl1 and Red1 core (MTREC)/PAXT complex nucleates Clr4/SUV39H at a heterochromatic long noncoding RNA (lncRNA) at which the two H3K9 deacetylases, Sir2 and Clr3, also accumulate by distinct mechanisms. Iterative cycles of H3K9 deacetylation and methylation spread Clr4/SUV39H from the nucleation center in an sRNA-independent manner, generating a basal H3K9me state. This is acted upon by the RNAi machinery to augment and amplify the Clr4/H3K9me signal at centromeres to establish heterochromatin. Overall, our data reveal that lncRNAs and RNA quality control factors can nucleate heterochromatin and function as epigenetic silencers in eukaryotes.

摘要

在真核生物中，Suv39 家族的蛋白质将组蛋白 H3 的赖氨酸 9 三甲基化（H3K9me），形成组成型异染色质。然而，Suv39 蛋白如何在异染色质上成核尚未完全描述。在裂殖酵母中，目前的模型假设 Argonaute1 相关的小 RNA（sRNA）将唯一的 H3K9 甲基转移酶 Clr4/SUV39H 核定于着丝粒。在这里，我们表明在没有所有 sRNA 和 H3K9me 的情况下，Mtl1 和 Red1 核心（MTREC）/PAXT 复合物通过不同的机制将 Clr4/SUV39H 核定于一个异染色质长非编码 RNA（lncRNA）上，两个 H3K9 去乙酰化酶 Sir2 和 Clr3 也在此积累。H3K9 去乙酰化和甲基化的反复循环以非 sRNA 依赖的方式将 Clr4/SUV39H 从成核中心扩散，产生基本的 H3K9me 状态。这被 RNAi 机制作用，以增强和放大着丝粒处的 Clr4/H3K9me 信号，从而建立异染色质。总的来说，我们的数据表明 lncRNA 和 RNA 质量控制因子可以核化异染色质，并在真核生物中作为表观遗传沉默因子发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/c156cb050777/nihms-2000812-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/09897602f8fa/nihms-2000812-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/faed5aa81011/nihms-2000812-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/1ecbd4e5c912/nihms-2000812-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/5018dec92b44/nihms-2000812-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/b0659bc64ecd/nihms-2000812-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/fb9f3edf5954/nihms-2000812-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/c156cb050777/nihms-2000812-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/09897602f8fa/nihms-2000812-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/faed5aa81011/nihms-2000812-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/1ecbd4e5c912/nihms-2000812-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/5018dec92b44/nihms-2000812-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/b0659bc64ecd/nihms-2000812-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/fb9f3edf5954/nihms-2000812-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b971/11227895/c156cb050777/nihms-2000812-f0008.jpg

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