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Updated: Jun 16, 2025
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A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model
Published on: February 6, 2018
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RNA helicase D1PAS1 resolves R-loops and forms a complex for mouse pachytene piRNA biogenesis required for male
Heejin Choi1, Lecong Zhou1, Yangu Zhao1
1Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Nucleic Acids Research
|August 20, 2024
Summary
The ATP-dependent RNA helicase D1PAS1 is essential for piRNA biogenesis in mice. Depletion of D1PAS1 disrupts piRNA production, causing male infertility due to spermatogenic arrest.
Area of Science:
- Reproductive biology
- Molecular genetics
- RNA biology
Background:
- Piwi-interacting RNAs (piRNAs) are crucial for male fertility and germline development.
- The transcription and maturation of piRNAs, particularly during meiosis, involve complex regulatory mechanisms.
- The precise role of transcriptional machinery in piRNA biogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the role of the ATP-dependent RNA helicase D1PAS1 in pachytene piRNA expression.
- To elucidate the molecular mechanisms by which D1PAS1 impacts piRNA biogenesis and male fertility.
- To identify D1PAS1 as a critical factor in the transcriptional regulation of piRNA precursors.
Main Methods:
- Gene editing in mice to deplete D1PAS1.
- Transcriptome analysis (RNA-seq).
- Genome-wide R-loop profiling.
- Proteomic analysis.
Main Results:
- D1PAS1 depletion causes R-loop accumulation in pachytene spermatocytes, leading to DNA damage and apoptosis.
- Loss of D1PAS1 disrupts piRNA precursor transcription, elongation, and termination.
- D1PAS1 is required for nuclear export of piRNA precursors for cytoplasmic processing.
- D1PAS1 deficiency results in spermatogenic arrest and male infertility.
Conclusions:
- D1PAS1 acts as a specific transcription activator essential for pachytene piRNA biogenesis.
- D1PAS1 unwinds R-loops, preventing DNA damage and promoting proper piRNA precursor processing.
- D1PAS1 is a critical regulator linking transcription, nuclear export, and piRNA maturation, ensuring male fertility.
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