The NIP proteins: Inhibitors of nuclear RNA interference

NIP 蛋白：核 RNA 干扰的抑制剂

• 批准号: RGPIN-2017-06311
• 负责人: Duchaine, Thomas
• 金额: $ 2.91万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629887
• 关键词: NIP; proteins; Inhibitors; nuclear; RNA

The RNA interference (RNAi) pathways instigate gene silencing through transcriptional and post-transcriptional mechanisms. SiRNAs of endogenous and exogenous origins are loaded onto specialized cytoplasmic and nuclear Argonautes, which in turn direct gene-silencing complexes. Loading of nuclear Argonautes results in their nuclear translocation, and in recruitment of effector complexes, which mediate the deposition of silencing chromatin marks on target loci. We discovered the family of uncharacterized Nuclear Argonaute-Interacting Proteins (NIP-1, NIP-2 will be examined), which stably interact with NRDE-3. NIP proteins encode a conserved P-loop containing nucleoside triphosphate hydrolase (NTPase) domain. Loss-of-function alleles specifically enhance nuclear RNAi and NIP-1 overexpression results in refraction, while having little effect on cytoplasmic RNAi targets. NIP-1 interacts with unloaded NRDE-3, and does not interact with small RNAs.

RNA干扰（RNAi）途径通过转录和转录后机制引发基因沉默。内源性和外源性sirna被装载到特定的细胞质和细胞核中，从而直接介导基因沉默复合物。核Argonautes的负载导致它们的核易位和效应复合物的招募，这些效应复合物介导沉默染色质标记在靶位点上的沉积。我们发现了与NRDE-3稳定相互作用的核argonaute相互作用蛋白家族（将研究nip1， nip2）。NIP蛋白编码一个保守的含有核苷三磷酸水解酶（NTPase）结构域的p环。功能缺失等位基因特异性增强核RNAi和NIP-1过表达导致折射，而对细胞质RNAi靶点影响不大。nip1与未加载的NRDE-3相互作用，不与小rna相互作用。