Cecchini Katharine, Ajaykumar Nandagopal, Bagci Ayca, Zamore Phillip D, Gainetdinov Ildar
RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Department of Biology, New York University, New York, NY 10003, USA.
bioRxiv. 2024 Nov 3:2024.11.02.621675. doi: 10.1101/2024.11.02.621675.
In animals, 18-35-nt piRNAs guide PIWI proteins to regulate complementary RNAs. During male meiosis, mammals produce an exceptionally abundant class of piRNAs called pachytene piRNAs. Pachytene piRNAs are required for spermatogenesis and have been proposed to control gene expression by various mechanisms. Here, we show that pachytene piRNAs regulate targets predominantly, if not exclusively, by endonucleolytic cleavage. Remarkably, pachytene piRNAs slice hundreds of RNAs, yet a change in steady-state level is detectable for a small fraction of transcripts. Our data suggest that cleavage of the few targets whose abundance is reduced significantly by piRNAs is essential for male fertility. Other pachytene piRNA targets are enriched for highly transcribed genes, which may explain why piRNA cleavage is often inconsequential for the steady-state abundance of targets. We propose that the retention of pachytene piRNAs throughout mammalian evolution is driven by the selective advantage conferred by a tiny minority of piRNAs.
在动物中，18 - 35个核苷酸的piRNA引导PIWI蛋白调控互补RNA。在雄性减数分裂期间，哺乳动物产生一类异常丰富的piRNA，称为粗线期piRNA。粗线期piRNA是精子发生所必需的，并且有人提出它们通过多种机制控制基因表达。在这里，我们表明粗线期piRNA主要（如果不是唯一的话）通过核酸内切酶切割来调控靶标。值得注意的是，粗线期piRNA切割数百种RNA，但只有一小部分转录本的稳态水平可检测到变化。我们的数据表明，少数被piRNA显著降低丰度的靶标的切割对于雄性生育力至关重要。其他粗线期piRNA靶标富含高转录基因，这可能解释了为什么piRNA切割通常对靶标的稳态丰度没有影响。我们提出，在整个哺乳动物进化过程中粗线期piRNA的保留是由极少数piRNA所赋予的选择优势驱动的。
