4.8 Article

Single-molecule long-read sequencing reveals a conserved intact long RNA profile in sperm

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NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21524-6

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  1. National Institute of General Medical Sciences [K99/R00HD078482]
  2. National Institute of Environmental Health Sciences [P30 ES001247-45]
  3. National Human Genome Research Institute [R01HG008759]
  4. Department of Biomedical Informatics, The Ohio State University
  5. Department of Internal Medicine, University of Iowa
  6. University of Rochester Center for RNA Biology

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This study successfully identified thousands of intact RNA species in mouse and human sperm, including both mRNAs and long non-coding RNAs, using single molecule long-read sequencing. These spiRNAs show evolutionary conservation between mice and humans.
Sperm contributes diverse RNAs to the zygote. While sperm small RNAs have been shown to impact offspring phenotypes, our knowledge of the sperm transcriptome, especially the composition of long RNAs, has been limited by the lack of sensitive, high-throughput experimental techniques that can distinguish intact RNAs from fragmented RNAs, known to abound in sperm. Here, we integrate single-molecule long-read sequencing with short-read sequencing to detect sperm intact RNAs (spiRNAs). We identify 3440 spiRNA species in mice and 4100 in humans. The spiRNA profile consists of both mRNAs and long non-coding RNAs, is evolutionarily conserved between mice and humans, and displays an enrichment in mRNAs encoding for ribosome. In sum, we characterize the landscape of intact long RNAs in sperm, paving the way for future studies on their biogenesis and functions. Our experimental and bioinformatics approaches can be applied to other tissues and organisms to detect intact transcripts. Sperm carry diverse RNAs to the zygote. Here the authors employ single molecule long-read sequencing to distinguish intact RNAs from fragmented RNAs, reporting thousands of intact sperm RNA species conserved in mouse and human sperms.

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