RNA quality control by CCR4 safeguards chromatin integrity and centromere function in Arabidopsis [EM-seq]. RNA quality control by CCR4 safeguards chromatin integrity and centromere function in Arabidopsis [EM-seq]

The centromere is a pivotal chromatin domain that ensures accurate chromosome segregation during cell division. However, the epigenome regulation of the centromere and its impact on centromere function remain largely elusive. Here in the model plant Arabidopsis, we show that CCR4, the catalytic subunit of the RNA deadenylation complex CCR4-NOT, is essential for maintenance of the centromere epigenome and chromosome integrity. We demonstrate that CCR4 is involved in shortening of the poly(A) tails of transcripts originated from centromeric transposons and repeats, thereby promoting the production of small interfering RNAs (siRNAs). The CCR4-dependent siRNAs guide non-CG DNA methylation at centromere repeats, and CCR4 cooperates with canonical DNA methylation pathways to enhance centromeric H3K9 methylation and ensure mitotic chromosome stability. Our study illustrates the crucial role of RNA quality control in RNA interference and reveals the elaborate mechanism that safeguards plant centromeres through epigenomic regulation. Overall design: Enzymatic Methyl-seq samples using 6-week-old leaves in WT, ccr4a ccr4b, ddm1rdr2, ddm1 rdr2 ccr4a ccr4b.

着丝粒是核心染色质结构域，可确保细胞分裂过程中染色体的精准分离。然而，着丝粒的表观基因组调控及其对着丝粒功能的影响目前仍未被充分解析。本研究以模式植物拟南芥（Arabidopsis）为材料，证实RNA脱腺苷化复合物CCR4-NOT的催化亚基CCR4对于维持着丝粒表观基因组与染色体完整性至关重要。研究表明，CCR4可介导着丝粒转座子与重复序列来源转录本的poly(A)尾缩短过程，进而促进小干扰RNA（small interfering RNAs, siRNAs）的生成。依赖CCR4的siRNAs可靶向引导着丝粒重复序列的非CG型DNA甲基化；同时，CCR4可与经典DNA甲基化通路协同作用，增强着丝粒区域的H3K9甲基化水平，保障有丝分裂染色体的稳定性。本研究阐明了RNA质量控制在RNA干扰中的核心作用，并揭示了通过表观基因组调控维持植物着丝粒稳态的精细调控机制。实验设计：以6周龄叶片为材料，对野生型（WT）、ccr4a ccr4b、ddm1rdr2以及ddm1 rdr2 ccr4a ccr4b四组样本开展酶解法甲基化测序（Enzymatic Methyl-seq）。