Shchepachev Vadim, Wischnewski Harry, Soneson Charlotte, Arnold Andreas W, Azzalin Claus M
Institute of Biochemistry (IBC), Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich CH-8093, Switzerland.
Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne CH-1015, Switzerland.
FEBS Lett. 2015 Aug 19;589(18):2417-23. doi: 10.1016/j.febslet.2015.06.046. Epub 2015 Jul 23.
Mpn1 is an exoribonuclease that modifies the spliceosomal small nuclear RNA (snRNA) U6 by trimming its oligouridine tail and introducing a cyclic phosphate group (>p). Mpn1 deficiency induces U6 3' end misprocessing, accelerated U6 decay and pre-mRNA splicing defects. Mutations in the human MPN1 gene are associated with the genodermatosis Clericuzio-type poikiloderma with neutropenia (PN). Here we present the deep sequencing of the >p-containing transcriptomes of mpn1Δ fission yeast and PN cells. While in yeast U6 seems to be the only substrate of Mpn1, human Mpn1 also processes U6atac snRNA. PN cells bear unstable U6atac species with aberrantly long and oligoadenylated 3' ends. Our data corroborate the link between Mpn1 and snRNA stability suggesting that PN could derive from pre-mRNA splicing aberrations.
Mpn1是一种外切核糖核酸酶，它通过修剪寡聚尿苷尾巴并引入环状磷酸基团（>p）来修饰剪接体小核RNA（snRNA）U6。Mpn1缺陷会导致U6 3'末端加工错误、U6加速降解以及前体mRNA剪接缺陷。人类MPN1基因的突变与伴有中性粒细胞减少症的遗传性皮肤病Clericuzio型皮肤异色症（PN）相关。在此，我们展示了对mpn1Δ裂殖酵母和PN细胞中含>p转录组的深度测序。在酵母中，U6似乎是Mpn1的唯一底物，而人类Mpn1也加工U6atac snRNA。PN细胞带有不稳定的U6atac种类，其3'末端异常长且带有寡聚腺苷酸化。我们的数据证实了Mpn1与snRNA稳定性之间的联系，表明PN可能源于前体mRNA剪接异常。
