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MIWI Prevents Aneuploidy during Meiosis by Cleaving Excess Satellite RNA

ABSTRACT: MIWI, a murine member of PIWI proteins mostly expressed during male meiosis, is crucial for piRNA biogenesis, post-transcriptional regulation, and spermiogenesis. However, its meiotic function remains unknown. Here we report that MIWI deficiency alters meiotic kinetochore assembly, significantly increases chromosome mis-alignment at the meiosis metaphase I plate, and causes chromosome mis-segregation. Consequently, Miwi-deficient mice show elevated aneuploidy in metaphase II and spermatid death. Furthermore, in Miwi-null and Miwi-slicer-deficient mutants, major and minor satellite RNAs from centromeric and pericentromeric satellite repeats accumulate in excess. Over-expression of satellite repeats in wild-type spermatocytes also causes elevated aneuploidy, whereas reduction of both strands of major or minor satellite RNAs results in lower frequencies of chromosome misalignment. We show that MIWI, guided by piRNA, cleaves major satellite RNAs, generating RNA fragments that may form substrates for subsequent Dicer cleavage. Furthermore, Dicer cleaves all satellite RNAs in conjunction with MIWI. These findings reveal a novel mechanism in which MIWI- and Dicer-mediated cleavage of the satellite RNAs prevents the over-expression of satellite RNAs, thus ensuring proper kinetochore assembly and faithful chromosome segregation during meiosis.

SUBMITTER: Dr. Chia-Ling Hsieh

PROVIDER: S-SCDT-EMBOJ-2019-103614P | biostudies-other |

REPOSITORIES: biostudies-other

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MIWI prevents aneuploidy during meiosis by cleaving excess satellite RNA.

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