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一项针对xrn-2抑制因子的种系靶向基因筛选在秀丽隐杆线虫中鉴定出一个新基因C34C12.2。

A germline-targeted genetic screen for xrn-2 suppressors identifies a novel gene C34C12.2 in Caenorhabditis elegans.

作者信息

Aygün Ilkin, Rzepczak Alicja, Miki Takashi S

机构信息

Polish Academy of Sciences, Institute of Bioorganic Chemistry, Department of Developmental Biology, Poznań, Poland.

出版信息

Genet Mol Biol. 2023 May 15;46(2):e20220328. doi: 10.1590/1678-4685-GMB-2022-0328. eCollection 2023.

DOI:10.1590/1678-4685-GMB-2022-0328
PMID:37216322
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10202090/
Abstract

XRN2 is an evolutionarily conserved 5'-to-3' exoribonuclease, which degrades or trims various types of RNA in the nucleus. Although XRN-2 is essential for embryogenesis, larval development and reproduction in Caenorhabditis elegans, relevant molecular pathways remain unidentified. Here we create a germline-specific xrn-2 conditional mutant and perform a mutagenesis screen for suppressors of sterility. Loss-of-function alleles of dpy-10, osr-1, ptr-6 and C34C12.2 genes are identified. Depletion of DPY-10, OSR-1 or PTR-6 increases expression of gpdh-1 that encodes a glycerol-3-phosphate dehydrogenase, thereby elevates glycerol accumulation to suppress sterility of the mutant. The C34C12.2 protein is predominantly localized in the nucleolus of germ cells and shows a similarity to Saccharomyces cerevisiae Net1, which is involved in rDNA silencing. Depletion of NRDE-2, a putative interacting partner of C34C12.2 and a component of the nuclear RNAi machinery, restores fertility to the xrn-2 conditional mutant. These results may help to identify an essential role of XRN-2 in germline development.

摘要

XRN2是一种进化上保守的5'至3'外切核糖核酸酶，可在细胞核中降解或修剪各种类型的RNA。尽管XRN-2对线虫的胚胎发生、幼虫发育和繁殖至关重要，但其相关分子途径仍未明确。在此，我们创建了一种生殖系特异性的xrn-2条件突变体，并对不育抑制因子进行了诱变筛选。鉴定出了dpy-10、osr-1、ptr-6和C34C12.2基因的功能缺失等位基因。DPY-10、OSR-1或PTR-6的缺失会增加编码甘油-3-磷酸脱氢酶的gpdh-1的表达，从而提高甘油积累以抑制突变体的不育性。C34C12.2蛋白主要定位于生殖细胞的核仁中，并且与参与rDNA沉默的酿酒酵母Net1具有相似性。NRDE-2是C34C12.2的假定相互作用伙伴和核RNAi机制的一个组成部分，其缺失可恢复xrn-2条件突变体的生育能力。这些结果可能有助于确定XRN-2在生殖系发育中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/10202090/71753e13f064/1415-4757-GMB-46-02-e20220328-gf4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/10202090/e3644f528ed4/1415-4757-GMB-46-02-e20220328-gf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/10202090/b0ef0318b2ff/1415-4757-GMB-46-02-e20220328-gf2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/10202090/47bb110b3fe7/1415-4757-GMB-46-02-e20220328-gf3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/10202090/71753e13f064/1415-4757-GMB-46-02-e20220328-gf4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/10202090/e3644f528ed4/1415-4757-GMB-46-02-e20220328-gf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/10202090/b0ef0318b2ff/1415-4757-GMB-46-02-e20220328-gf2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/10202090/47bb110b3fe7/1415-4757-GMB-46-02-e20220328-gf3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/10202090/71753e13f064/1415-4757-GMB-46-02-e20220328-gf4.jpg

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本文引用的文献

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