MIWI N-terminal arginines orchestrate generation of functional pachytene piRNAs and spermiogenesis.
Nucleic Acids Res
; 52(11): 6558-6570, 2024 Jun 24.
Article
em En
| MEDLINE
| ID: mdl-38520410
ABSTRACT
N-terminal arginine (NTR) methylation is a conserved feature of PIWI proteins, which are central components of the PIWI-interacting RNA (piRNA) pathway. The significance and precise function of PIWI NTR methylation in mammals remains unknown. In mice, PIWI NTRs bind Tudor domain containing proteins (TDRDs) that have essential roles in piRNA biogenesis and the formation of the chromatoid body. Using mouse MIWI (PIWIL1) as paradigm, we demonstrate that the NTRs are essential for spermatogenesis through the regulation of transposons and gene expression. The loss of TDRD5 and TDRKH interaction with MIWI results in attenuation of piRNA amplification. We find that piRNA amplification is necessary for transposon control and for sustaining piRNA levels including select, nonconserved, pachytene piRNAs that target specific mRNAs required for spermatogenesis. Our findings support the notion that the vast majority of pachytene piRNAs are dispensable, acting as self-serving genetic elements that rely for propagation on MIWI piRNA amplification. MIWI-NTRs also mediate interactions with TDRD6 that are necessary for chromatoid body compaction. Furthermore, MIWI-NTRs promote stabilization of spermiogenic transcripts that drive nuclear compaction, which is essential for sperm formation. In summary, the NTRs underpin the diversification of MIWI protein function.
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Base de dados:
MEDLINE
Assunto principal:
Arginina
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Espermatogênese
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RNA Interferente Pequeno
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Estágio Paquíteno
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Proteínas Argonautas
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article