Department of Biochemistry and Molecular Biology, SUNY-Upstate Medical University, Syracuse, NY, USA.
Wiley Interdiscip Rev RNA. 2012 Sep-Oct;3(5):633-47. doi: 10.1002/wrna.1123. Epub 2012 Jun 27.
Bicoid-interacting protein 3 (Bin3) is a conserved RNA methyltransferase found in eukaryotes ranging from fission yeast to humans. It was originally discovered as a Bicoid (Bcd)-interacting protein in Drosophila, where it is required for anterior-posterior and dorso-ventral axis determination in the early embryo. The mammalian ortholog of Bin3 (BCDIN3), also known as methyl phosphate capping enzyme (MePCE), plays a key role in repressing transcription. In transcription, MePCE binds the non-coding 7SK RNA, which forms a scaffold for an RNA-protein complex that inhibits positive-acting transcription elongation factor b, an RNA polymerase II elongation factor. MePCE uses S-adenosyl methionine to transfer a methyl group onto the γ-phosphate of the 5' guanosine of 7SK RNA generating an unusual cap structure that protects 7SK RNA from degradation. Bin3/MePCE also has a role in translation regulation. Initial studies in Drosophila indicate that Bin3 targets 7SK RNA and stabilizes a distinct RNA-protein complex that assembles on the 3'-untranslated region of caudal mRNAs to prevent translation initiation. Much remains to be learned about Bin3/MeCPE function, including how it recognizes 7SK RNA, what other RNA substrates it might target, and how widespread a role it plays in gene regulation and embryonic development.
双翅目昆虫间隔蛋白 3（Bin3）是一种在真核生物中广泛存在的保守 RNA 甲基转移酶，从裂殖酵母到人类都有。它最初在果蝇中被发现是一种与 Bicoid（Bcd）相互作用的蛋白质，在早期胚胎中，它对于前后轴和背腹轴的确定是必需的。Bin3 的哺乳动物同源物（BCDIN3），也称为磷酸甲酯封端酶（MePCE），在转录抑制中起着关键作用。在转录过程中，MePCE 结合非编码 7SK RNA，形成一个 RNA-蛋白质复合物的支架，抑制正向转录延伸因子 b，即 RNA 聚合酶 II 延伸因子。MePCE 利用 S-腺苷甲硫氨酸将一个甲基转移到 7SK RNA 的 5' 鸟苷的 γ-磷酸上，生成一种不寻常的帽结构，保护 7SK RNA 免受降解。Bin3/MePCE 也在翻译调节中发挥作用。在果蝇中的初步研究表明，Bin3 靶向 7SK RNA，并稳定一个独特的 RNA-蛋白质复合物，该复合物在尾部 mRNA 的 3' 非翻译区组装，以防止翻译起始。关于 Bin3/MeCPE 的功能还有很多需要了解的地方，包括它如何识别 7SK RNA，它可能靶向哪些其他 RNA 底物，以及它在基因调控和胚胎发育中的作用有多广泛。
