Circular RNAs from BOULE play conserved roles in protection against stress-induced fertility decline.

Circular RNAs from BOULE play conserved roles in protection against stress-induced fertility decline.
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BOULE 的环状 RNA 在防止压力引起的生育能力下降方面发挥保守作用

DOI:
10.1126/sciadv.abb7426
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发表时间:
2020-11
期刊:
影响因子:
13.6
通讯作者:
Shan G
Shan G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gao L;Chang S;Xia W;Wang X;Zhang C;Cheng L;Liu X;Chen L;Shi Q;Huang J;Xu EY;Shan G

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保守的环状rna保护动物雄性生育力免受热损伤。环状rna (circRNAs)是一个新发现的转录本大家族,其生理作用和进化意义需要进一步表征。在这里,我们在从果蝇到人类的物种中鉴定了由保守的生殖基因Boule产生的环状rna。在热应激条件下,缺少环状Boule (circBoule) rna的果蝇表现出雄性生育能力下降,而敲除环状Boule的小鼠精子表现出受精能力下降。在精子发生过程中,果蝇cirboule rna与热休克蛋白(HSPs) Hsc4和Hsp60C相互作用,小鼠精子中的cirboule rna与HSPA2相互作用。环状rna通过促进热休克蛋白的泛素化来调节其水平。HSPA2和circbole rna之间的相互作用在人类精子中是保守的,在弱动精子中发现较低水平的人类circEx3-6和circEx2-7。我们的研究结果揭示了cirboule rna在后生动物中的保守生理功能,并表明特定的circRNAs可能是动物雄性生殖功能抵抗应激的关键调节剂。
Conserved circBoule RNAs protect male fertility from thermal insults in animals. Circular RNAs (circRNAs) are a large family of newly identified transcripts, and their physiological roles and evolutionary significance require further characterization. Here, we identify circRNAs generated from a conserved reproductive gene, Boule, in species from Drosophila to humans. Flies missing circular Boule (circBoule) RNAs display decreased male fertility, and sperm of circBoule knockout mice exhibit decreased fertilization capacity, when under heat stress conditions. During spermatogenesis, fly circBoule RNAs interact with heat shock proteins (HSPs) Hsc4 and Hsp60C, and mouse circBoule RNAs in sperm interact with HSPA2. circBoule RNAs regulate levels of HSPs by promoting their ubiquitination. The interaction between HSPA2 and circBoule RNAs is conserved in human sperm, and lower levels of the human circBoule RNAs circEx3-6 and circEx2-7 are found in asthenozoospermic sperm. Our findings reveal conserved physiological functions of circBoule RNAs in metazoans and suggest that specific circRNAs may be critical modulators of male reproductive function against stresses in animals.
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