RNAPII-CTD 的 Ser7 可通过将 ncRNA 与 RNAi 连接来促进异染色质形成。
Ser7 of RNAPII-CTD facilitates heterochromatin formation by linking ncRNA to RNAi.
机构信息
Graduate School of Science, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan;
Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
出版信息
Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):E11208-E11217. doi: 10.1073/pnas.1714579115. Epub 2017 Dec 13.
Some long noncoding RNAs (ncRNAs) transcribed by RNA polymerase II (RNAPII) are retained on chromatin, where they regulate RNAi and chromatin structure. The molecular basis of this retention remains unknown. We show that in fission yeast serine 7 (Ser7) of the C-terminal domain (CTD) of RNAPII is required for efficient siRNA generation for RNAi-dependent heterochromatin formation. Surprisingly, Ser7 facilitates chromatin retention of nascent heterochromatic RNAs (hRNAs). Chromatin retention of hRNAs and siRNA generation requires both Ser7 and an RNA-binding activity of the chromodomain of Chp1, a subunit of the RNA-induced transcriptional silencing (RITS) complex. Furthermore, RITS associates with RNAPII in a Ser7-dependent manner. We propose that Ser7 promotes cotranscriptional chromatin retention of hRNA by recruiting the RNA-chromatin connector protein Chp1, which facilitates RNAi-dependent heterochromatin formation. Our findings reveal a function of the CTD code: linking ncRNA transcription to RNAi for heterochromatin formation.
一些由 RNA 聚合酶 II（RNAPII）转录的长非编码 RNA（ncRNA）保留在染色质上，在那里它们调节 RNAi 和染色质结构。这种保留的分子基础尚不清楚。我们表明，在裂殖酵母中，RNA 聚合酶 II C 末端结构域（CTD）上的丝氨酸 7（Ser7）是 RNAi 依赖性异染色质形成中有效产生 siRNA 所必需的。令人惊讶的是，Ser7 促进了新生异染色质 RNA（hRNA）的染色质保留。hRNA 的染色质保留和 siRNA 的产生既需要 Ser7，也需要 Chp1 的 chromodomain 的 RNA 结合活性，Chp1 是 RNA 诱导的转录沉默（RITS）复合物的一个亚基。此外，RITS 以 Ser7 依赖性的方式与 RNAPII 相关联。我们提出，Ser7 通过招募 RNA-染色质连接蛋白 Chp1 促进 hRNA 的共转录染色质保留，从而促进 RNAi 依赖性异染色质形成。我们的发现揭示了 CTD 编码的一个功能：将 ncRNA 转录与 RNAi 联系起来，以形成异染色质。
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