Kastor and Polluks polypeptides encoded by a single gene locus cooperatively regulate VDAC and spermatogenesis.

Kastor and Polluks polypeptides encoded by a single gene locus cooperatively regulate VDAC and spermatogenesis.
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DOI:
10.1038/s41467-022-28677-y
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发表时间:
2022-02-28
影响因子:
16.6
通讯作者:
Nakayama KI
Nakayama KI
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mise S;Matsumoto A;Shimada K;Hosaka T;Takahashi M;Ichihara K;Shimizu H;Shiraishi C;Saito D;Suyama M;Yasuda T;Ide T;Izumi Y;Bamba T;Kimura-Someya T;Shirouzu M;Miyata H;Ikawa M;Nakayama KI

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虽然最近发现了几种长链非编码RNA(lncRNA)编码小分子多肽,但睾丸中的lncRNA在很大程度上还没有被鉴定。在这里,我们鉴定了两种精子特异性多肽Kastor和Pollouks,它们由先前注释为编码lncRNA的单个小鼠基因座(Gm9999)编码。尽管Kastor和Pollouks的氨基酸序列不同,但它们都插入线粒体外膜,并直接与电压依赖性阴离子通道(VDAC)相互作用。雄性VDAC 3缺陷小鼠由于精子中异常线粒体鞘导致精子活力降低而不育,Kastor和Pollouks缺陷也严重损害了与形成类似异常线粒体鞘相关的雄性生育力。缺少Kastor或Pollouks的精子部分地再现了缺少两者的精子的表型。因此,Kastor和Pollouks在调节VDAC 3中的合作功能可能对精子中线粒体鞘的形成和男性生育力至关重要。许多测试特异性lncRNA已被注释,但它们的作用仍然在很大程度上未被探索。在这里,作者鉴定了由lncRNA Gm9999编码的两种小肽,Kastor和Pollouks,这两种肽都是小鼠雄性生育所必需的。
Although several long noncoding RNAs (lncRNAs) have recently been shown to encode small polypeptides, those in testis remain largely uncharacterized. Here we identify two sperm-specific polypeptides, Kastor and Polluks, encoded by a single mouse locus (Gm9999) previously annotated as encoding a lncRNA. Both Kastor and Polluks are inserted in the outer mitochondrial membrane and directly interact with voltage-dependent anion channel (VDAC), despite their different amino acid sequences. Male VDAC3-deficient mice are infertile as a result of reduced sperm motility due to an abnormal mitochondrial sheath in spermatozoa, and deficiency of both Kastor and Polluks also severely impaired male fertility in association with formation of a similarly abnormal mitochondrial sheath. Spermatozoa lacking either Kastor or Polluks partially recapitulate the phenotype of those lacking both. Cooperative function of Kastor and Polluks in regulation of VDAC3 may thus be essential for mitochondrial sheath formation in spermatozoa and for male fertility. A number of testes-specific lncRNAs have been annotated but their roles remain largely unexplored. Here the authors identify two small peptides encoded by the lncRNA Gm9999, Kastor and Polluks, both of which are required for male fertility in mice.
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