香港科技大学Tuan Anh Nguyen团队在研究中取得进展。他们提出了DICER切割保真度由5'端结合口袋控制。这一研究成果发表在2026年3月4日出版的国际学术期刊《自然》上。

这里研究小组发现5' -G促进了许多底物的精确切割。利用大量平行切片分析和低温电镜，该课题组在DICER中发现了一个保守的鸟苷（G-favtheired）结合袋，与之前描述的尿苷（U-favtheired）结合袋不同。总之，这些口袋影响了21-核苷酸和22-核苷酸切割寄存器之间的对齐，扩展了后生动物DICERs中小RNA生物发生的机制。

该课题组研究人员还发现，5'端结合和RNA基序识别之间的冲突可以触发RNA构象调整，从而保持准确的切割位点选择。此外，双链RNA结合域（dsRBD）和PAZ结构域的构象调整有助于将底物与催化中心对齐，以实现精确的双链切割。这些结果表明DICER的切割机制整合了双5'端结合口袋、RNA-motif影响和结构域运动，促进了他们对microRNA生物发生的理解。

研究人员表示，RNA干扰（RNAi）依赖于DICER， DICER是一种将RNA前体加工成小调控RNA的基本酶。DICER根据5'端计数规则切割RNA前体，其中RNA长度从5'端开始测量。先前的研究提出了一个单一的5'端结合袋，它不利于鸟苷（5'-G），导致切割不准确。

附：英文原文

Title: DICER cleavage fidelity is governed by 5′-end binding pockets

Author: Ngo, Minh Khoa, Le, Cong Truc, Nguyen, Tuan Anh

Issue&Volume: 2026-03-04

Abstract: RNA interference (RNAi) depends on DICER, an essential enzyme that processes RNA precursors into small regulatory RNAs. DICER cleaves RNA precursors according to the 5′-end counting rule, in which RNA length is measured from the 5′-end1,2,3. Previous work proposed a single 5′-end binding pocket that disfavours guanosine (5′-G), leading to cleavage inaccuracies4. Here we show that 5′-G promotes precise cleavage for many substrates. Using massively parallel dicing assays and cryo-electron microscopy, we identify a conserved guanosine-favoured (G-favoured) binding pocket in DICER, distinct from the previously described uridine-favoured (U-favoured) pocket. Together, these pockets influence the alignment between 21-nucleotide and 22-nucleotide cleavage registers, expanding the mechanism of small-RNA biogenesis in metazoan DICERs. We also find that conflicts between 5′-end binding and RNA-motif recognition can trigger RNA conformational adjustments that preserve accurate cleavage-site selection. In addition, conformational adjustments of the double-stranded RNA-binding domain (dsRBD) and PAZ domain help to align substrates with the catalytic centres for precise double-strand cleavage. These results show that the DICER cleavage mechanism integrates dual 5′-end binding pockets, RNA-motif influence and domain motions, advancing our understanding of microRNA biogenesis.

DOI: 10.1038/s41586-026-10211-5

Source: https://www.nature.com/articles/s41586-026-10211-5