Institut de Biologie Moléculaire des Plantes, CNRS, Université de Strasbourg, Strasbourg, F-67084, France.
Plant Molecular and Cellular Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Nat Commun. 2024 Nov 27;15(1):10298. doi: 10.1038/s41467-024-54268-0.
Eukaryotes must balance the need for gene transcription by RNA polymerase II (Pol II) against the danger of mutations caused by transposable element (TE) proliferation. In plants, these gene expression and TE silencing activities are divided between different RNA polymerases. Specifically, RNA polymerase IV (Pol IV), which evolved from Pol II, transcribes TEs to generate small interfering RNAs (siRNAs) that guide DNA methylation and block TE transcription by Pol II. While the Pol IV complex is recruited to TEs via SNF2-like CLASSY (CLSY) proteins, how Pol IV partners with the CLSYs remains unknown. Here, we identified a conserved CYC-YPMF motif that is specific to Pol IV and is positioned on the complex exterior. Furthermore, we found that this motif is essential for the co-purification of all four CLSYs with Pol IV, but that only one CLSY is present in any given Pol IV complex. These findings support a "one CLSY per Pol IV" model where the CYC-YPMF motif acts as a CLSY-docking site. Indeed, mutations in and around this motif phenocopy pol iv null and clsy quadruple mutants. Together, these findings provide structural and functional insights into a critical protein feature that distinguishes Pol IV from other RNA polymerases, allowing it to promote genome stability by targeting TEs for silencing.
真核生物必须在 RNA 聚合酶 II(Pol II)的基因转录需求与转座元件(TE)增殖引起的突变危险之间取得平衡。在植物中,这些基因表达和 TE 沉默活性由不同的 RNA 聚合酶分担。具体而言,由 Pol II 进化而来的 RNA 聚合酶 IV(Pol IV)转录 TE 以产生小干扰 RNA(siRNA),这些 siRNA 指导 DNA 甲基化并阻止 Pol II 转录 TE。虽然 Pol IV 复合物通过 SNF2 样 CLASSY(CLSY)蛋白被招募到 TE 上,但 Pol IV 如何与 CLSY 相互作用仍然未知。在这里,我们鉴定了一个保守的 CYC-YPMF 基序,该基序是 Pol IV 特有的,位于复合物的外部。此外,我们发现该基序对于 Pol IV 与所有四个 CLSY 的共纯化至关重要,但任何给定的 Pol IV 复合物中仅存在一个 CLSY。这些发现支持了“一个 Pol IV 对应一个 CLSY”的模型,其中 CYC-YPMF 基序充当 CLSY docking 位点。事实上,该基序内或周围的突变与 pol iv 缺失和 clsy 四重突变体的表型相同。这些发现为区分 Pol IV 与其他 RNA 聚合酶的关键蛋白特征提供了结构和功能见解,使它能够通过靶向 TE 沉默来促进基因组稳定性。