Department of Cell and Molecular Biology, The University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Department of Cell and Molecular Biology, The University of Mississippi Medical Center, Jackson, MS 39216-4505, USA
Biol Open. 2020 Oct 26;9(10):bio054619. doi: 10.1242/bio.054619.
The Cajal body (CB) is a subnuclear domain that participates in the biogenesis of many different types of ribonucleoproteins (RNPs), including small nuclear RNPs (snRNPs), small Cajal body-specific RNPs (scaRNPs) and telomerase. Most scaRNAs, the RNA component of scaRNPs, accumulate in CBs. However, there are three scaRNAs (scaRNA 2, 9, and 17) that are known to be processed into small, nucleolar-enriched fragments. Evidence suggests that these fragments are packaged into a new class of RNPs, called regulatory RNPs (regRNPs), and may modify small nucleolar RNP (snoRNP) activity, thus playing a role in rRNA modification. However, the mechanism by which these fragments are produced is unknown. Previous work has reported the involvement of Drosha and DGCR8 in the cleavage of primary-scaRNA9. Here, we expand on that knowledge by identifying sequence elements necessary for the efficient production of these RNA fragments and demonstrate that primary scaRNA 2 and 17 are also processed by the Drosha-DGCR8 complex. Collectively, our work establishes new factors in the scaRNP biogenesis pathway and adds to the ever-expanding list of noncanonical functions for the microprocessor complex.
Cajal 体(CB)是一个亚核结构域,参与多种不同类型的核糖核蛋白(RNP)的生物发生,包括小核 RNP(snRNP)、小 Cajal 体特异性 RNP(scaRNP)和端粒酶。大多数 scaRNA,即 scaRNP 的 RNA 成分,在 CB 中积累。然而,有三种 scaRNA(scaRNA2、9 和 17)已知被加工成小的核仁丰富片段。有证据表明,这些片段被包装成一种新的 RNP 类,称为调节 RNP(regRNP),可能修饰小核仁 RNP(snoRNP)的活性,从而在 rRNA 修饰中发挥作用。然而,这些片段产生的机制尚不清楚。以前的工作已经报道了 Drosha 和 DGCR8 参与了初级 scaRNA9 的切割。在这里,我们通过鉴定有效产生这些 RNA 片段所需的序列元件扩展了这一知识,并证明初级 scaRNA2 和 17 也被 Drosha-DGCR8 复合物加工。总的来说,我们的工作确定了 scaRNP 生物发生途径中的新因子,并为微处理器复合物的非规范功能不断扩展的列表增添了新的内容。