Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Whitehead Institute of Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Whitehead Institute of Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mol Cell. 2020 Apr 16;78(2):289-302.e6. doi: 10.1016/j.molcel.2020.01.026.
Microprocessor initiates the processing of microRNAs (miRNAs) from the hairpin regions of primary transcripts (pri-miRNAs). Pri-miRNAs often contain multiple miRNA hairpins, and this clustered arrangement can assist in the processing of otherwise defective hairpins. We find that miR-451, which derives from a hairpin with a suboptimal terminal loop and a suboptimal stem length, accumulates to 40-fold higher levels when clustered with a helper hairpin. This phenomenon tolerates changes in hairpin order, linker lengths, and the identities of the helper hairpin, the recipient hairpin, the linker-sequence, and the RNA polymerase that transcribes the hairpins. It can act reciprocally and need not occur co-transcriptionally. It requires Microprocessor recognition of the helper hairpin and linkage of the two hairpins, yet predominantly manifests after helper-hairpin processing. It also requires enhancer of rudimentary homolog (ERH), which copurifies with Microprocessor and can dimerize and interact with other proteins that can dimerize, suggesting a model in which one Microprocessor recruits another Microprocessor.
微处理器启动从小核糖核酸（miRNAs）前体转录物（pri-miRNAs）的发夹区域加工 microRNAs（miRNAs）。pri-miRNAs 通常包含多个 miRNA 发夹，这种簇状排列有助于加工 otherwise defective hairpins。我们发现，miR-451 来源于具有次优末端环和次优茎长的发夹，当与辅助发夹簇集时，积累到 40 倍的更高水平。这种现象容忍发夹顺序、连接长度以及辅助发夹、受体发夹、连接序列和转录发夹的 RNA 聚合酶的变化。它可以相互作用，并且不必发生共转录。它需要 Microprocessor 识别辅助发夹并连接两个发夹，但主要发生在辅助发夹加工之后。它还需要基本同源物增强子（ERH），它与 Microprocessor 共纯化，并可以二聚化并与其他可以二聚化的蛋白质相互作用，表明一个 Microprocessor 招募另一个 Microprocessor 的模型。
