Knockout of the mitoribosome rescue factors Ict1 or Mtrfr is viable in zebrafish but not mice: compensatory mechanisms underlying each factor's loss.

IF 2.8 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Nobukazu Nameki, Chika Tomisawa, Soichiro Hoshino, Hidehiko Shimizu, Masashi Abe, Sho Arai, Kanako Kuwasako, Naoki Asakawa, Yusuke Inoue, Takuro Horii, Izuho Hatada, Masakatsu Watanabe
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引用次数: 0

Abstract

The mitochondrial translation system contains two ribosome rescue factors, ICT1 and MTRFR (C12orf65), which hydrolyze peptidyl-tRNA in stalled ribosomes. ICT1 also functions as a ribosomal protein of the mitochondrial large ribosomal subunit (mtLSU) in mice and humans, and its deletion is lethal. In contrast, MTRFR does not share this role. Although loss-of-function mutations in MTRFR have been linked to human mitochondrial diseases, data on this association in other vertebrates are lacking. Here, attempts to generate Mtrfr knockout mice were unsuccessful. However, knockout zebrafish lines were successfully generated for both ict1 and mtrfr (ict1-/- and mtrfr-/-). Both knockout lines appeared healthy and fertile. ict1-/-, mtrfr-/-, and wild-type adult caudal fin cells showed significant differences in mitochondrial morphology. The ict1 deletion affected the network properties more than the number of individuals and networks, whereas the mtrfr deletion exhibited the opposite effect. Additionally, the survival rates of the knockout line larvae were significantly lower than those of the wild-type larvae under starvation conditions. These results suggest that ict1 and mtrfr are required for survival under specific stress conditions, whereas ict1-/- and mtrfr-/- involve different compensatory mechanisms in response to loss of either factor under nonstress conditions. Ict1 proteins from all teleosts, including zebrafish, lack the N-terminal mtLSU-binding motif found in most metazoans, suggesting that Ict1 does not function as a ribosomal protein in teleosts. Thus, Mtrfr may partially compensate for the loss of Ict1. In conclusion, zebrafish appear to exemplify a limited category of vertebrates capable of enduring genetic abnormalities in ict1 or mtrfr.

敲除线粒体拯救因子Ict1或Mtrfr在斑马鱼中是可行的,但在小鼠中不可行:每种因子损失背后的补偿机制。
线粒体翻译系统包含两个核糖体救援因子ICT1和MTRFR (C12orf65),它们水解停滞核糖体中的肽基trna。在小鼠和人类中,ICT1还作为线粒体大核糖体亚基(mtLSU)的核糖体蛋白,其缺失是致命的。相比之下,MTRFR不承担这一角色。尽管MTRFR中的功能丧失突变与人类线粒体疾病有关,但在其他脊椎动物中缺乏这种关联的数据。在这里,试图产生Mtrfr敲除小鼠是不成功的。然而,成功地产生了ict1和mtrfr基因敲除的斑马鱼系(ict1-/-和mtrfr-/-)。两个基因敲除系都表现出健康和可育性。Ict1 -/-、mtrfr-/-和野生型成年尾鳍细胞线粒体形态存在显著差异。ict1缺失对网络特性的影响大于个体数量和网络数量,而mtrfr缺失则表现出相反的效果。此外,在饥饿条件下,敲除系幼虫的存活率显著低于野生型幼虫。这些结果表明,在特定的应激条件下,ict1和mtrfr是生存所必需的,而在非应激条件下,ict1-/-和mtrfr-/-涉及不同的补偿机制,以响应任何一个因子的丧失。来自所有硬骨鱼(包括斑马鱼)的Ict1蛋白缺乏在大多数后生动物中发现的n端mtlsu结合基元,这表明Ict1在硬骨鱼中不作为核糖体蛋白起作用。因此,mtfr可以部分补偿Ict1的损失。总之,斑马鱼似乎是能够忍受ict1或mtfr基因异常的有限种类脊椎动物的例证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
FEBS Open Bio
FEBS Open Bio BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
5.10
自引率
0.00%
发文量
173
审稿时长
10 weeks
期刊介绍: FEBS Open Bio is an online-only open access journal for the rapid publication of research articles in molecular and cellular life sciences in both health and disease. The journal''s peer review process focuses on the technical soundness of papers, leaving the assessment of their impact and importance to the scientific community. FEBS Open Bio is owned by the Federation of European Biochemical Societies (FEBS), a not-for-profit organization, and is published on behalf of FEBS by FEBS Press and Wiley. Any income from the journal will be used to support scientists through fellowships, courses, travel grants, prizes and other FEBS initiatives.
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