SAFB2 Enables the Processing of Suboptimal Stem-Loop Structures in Clustered Primary miRNA Transcripts
SAFB2 Enables the Processing of Suboptimal Stem-Loop Structures in Clustered Primary miRNA Transcripts
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DOI：
10.1016/j.molcel.2020.05.011
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发表时间：
2020-06-04
期刊：
影响因子：
16
通讯作者：
Herzog, Sebastian
中科院分区：
文献类型：
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作者：
Hutter, Katharina;Lohmueller, Michael;Herzog, Sebastian
许多microRNA（miRNAs）是由含有多个成簇茎环结构的初级转录物产生的，这些结构被认为是被微处理器复合物识别和切割为独立单元的。在这里，我们发现了一种意想不到的双顺反子miR-15 a-16-1簇的加工模式。我们发现，主要的miR-15 a茎环本身并不加工，但在同一转录本上相邻的主要miR-16-1茎环的存在可以弥补这种顺式缺陷。使用CRISPR/Cas9筛选，我们将SAFB 2（支架附着因子B2）鉴定为这种miR-16-1辅助的pri-miR-15切割中的必需辅因子，并将SAFB 2描述为微处理器的辅助蛋白。值得注意的是，SAFB 2介导的切割扩展到其他成簇的pri-miRNA，表明了一种通用机制。总之，我们的研究揭示了SAFB 2在miRNA加工中未被识别的功能，并提出了SAFB 2能够在成簇的初级miRNA转录物中结合和加工次优微处理器底物的情况。
Many microRNAs (miRNAs) are generated from primary transcripts containing multiple clustered stem-loop structures that are thought to be recognized and cleaved by the Microprocessor complex as independent units. Here, we uncover an unexpected mode of processing of the bicistronic miR-15a-16-1 cluster. We find that the primary miR-15a stem-loop is not processed on its own but that the presence of the neighboring primary miR-16-1 stem-loop on the same transcript can compensate for this deficiency in cis. Using a CRISPR/Cas9 screen, we identify SAFB2 (scaffold attachment factor B2) as an essential co-factor in this miR-16-1-assisted pri-miR-15 cleavage and describe SAFB2 as an accessory protein of the Microprocessor. Notably, SAFB2-mediated cleavage expands to other clustered pri-miRNAs, indicating a generalmechanism. Together, our study reveals an unrecognized function of SAFB2 in miRNA processing and suggests a scenario in which SAFB2 enables the binding and processing of suboptimal Microprocessor substrates in clustered primary miRNA transcripts.