Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Bioinformatics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Rep. 2020 Feb 25;30(8):2686-2698.e8. doi: 10.1016/j.celrep.2020.01.094.
Heterochromatin functions as a scaffold for factors responsible for gene silencing and chromosome segregation. Heterochromatin can be assembled by multiple pathways, including RNAi and RNA surveillance. We identified factors that form heterochromatin using dense profiles of transposable element integration in Schizosaccharomyces pombe. The candidates include a large number of essential proteins such as four canonical mRNA cleavage and polyadenylation factors. We find that Iss1, a subunit of the poly(A) polymerase module, plays a role in forming heterochromatin in centromere repeats that is independent of RNAi. Genome-wide maps reveal that Iss1 accumulates at genes regulated by RNA surveillance. Iss1 interacts with RNA surveillance factors Mmi1 and Rrp6, and importantly, Iss1 contributes to RNA elimination that forms heterochromatin at meiosis genes. Our profile of transposable element integration supports the model that a network of mRNA cleavage and polyadenylation factors coordinates RNA surveillance, including the mechanism that forms heterochromatin at meiotic genes.
异染色质作为负责基因沉默和染色体分离的因子的支架发挥作用。异染色质可以通过多种途径组装，包括 RNAi 和 RNA 监测。我们使用密集的转座元件整合图谱鉴定了形成异染色质的因子，这些候选因子包括大量必需蛋白，如四个经典的 mRNA 切割和多聚腺苷酸化因子。我们发现，多(A)聚合酶模块的亚基 Iss1 在着丝粒重复形成 RNAi 独立的异染色质中起作用。全基因组图谱显示，Iss1 在受 RNA 监测调控的基因处积累。Iss1 与 RNA 监测因子 Mmi1 和 Rrp6 相互作用，重要的是，Iss1 有助于在减数分裂基因处形成异染色质的 RNA 消除。我们的转座元件整合图谱支持这样一种模型，即一个 mRNA 切割和多聚腺苷酸化因子的网络协调 RNA 监测，包括在减数分裂基因处形成异染色质的机制。
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