Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA.
Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14787-92. doi: 10.1073/pnas.1009490107. Epub 2010 Aug 2.
5'-mRNA capping is an early modification that affects pre-mRNA synthesis/splicing, RNA cytoplasmic transport, and mRNA translation and turnover. In eukaryotes, a 7-methylguanosine (m7G) cap is added to newly transcribed RNA polymerase II (RNAP II) transcripts. A subset of RNAP II-transcribed cellular RNAs, including small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), and telomerase RNA, is further hypermethylated at the exocyclic N2 of the guanosine to create a trimethylguanosine (TMG)-capped RNA. Some of these TMG-capped RNAs are transported within the nucleus and from the nucleus to the cytoplasm by the CRM-1 (required for chromosome region maintenance) protein. CRM-1 is also used to export Rev/RRE-dependent unspliced/ partially spliced HIV-1 RNAs. Here we report that like snRNAs and snoRNAs, some Rev/RRE-dependent HIV-1 RNAs are TMG-capped. The methyltransferase responsible for TMG modification of HIV-1 RNAs is the human PIMT (peroxisome proliferator-activated receptor-interacting protein with methyltransferase) protein. TMG capping of unspliced/partially spliced HIV-1 RNAs represents a new regulatory mechanism for selective expression.
5'-mRNA 加帽是一种早期修饰，影响前体 mRNA 的合成/剪接、RNA 胞质运输以及 mRNA 的翻译和周转。在真核生物中，新转录的 RNA 聚合酶 II (RNAP II) 转录本会被加上 7-甲基鸟苷 (m7G) 帽。包括小核 RNA (snRNA)、小核仁 RNA (snoRNA) 和端粒酶 RNA 在内的一组 RNAP II 转录的细胞 RNA 进一步在鸟苷的外环 N2 上高度甲基化，形成三甲基鸟苷 (TMG) 帽 RNA。其中一些 TMG 帽 RNA 通过 CRM-1（维持染色体区域所必需的）蛋白在核内和从核内运输到细胞质。CRM-1 还用于输出依赖 Rev/RRE 的未剪接/部分剪接的 HIV-1 RNA。在这里，我们报告说，像 snRNA 和 snoRNA 一样，一些依赖 Rev/RRE 的 HIV-1 RNA 是 TMG 帽 RNA。负责 HIV-1 RNA TMG 修饰的甲基转移酶是人类 PIMT（过氧化物酶体增殖物激活受体相互作用蛋白具有甲基转移酶）蛋白。未剪接/部分剪接的 HIV-1 RNA 的 TMG 帽化代表了选择性表达的新调节机制。
