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Piwi-Interacting RNAs Inherited From Fly Moms Can Direct Epigenetics

NEW YORK (GenomeWeb News) – A new fruit fly study suggests small RNAs passed from mothers to embryos participate in epigenetic inheritance.
Researchers from Cold Spring Harbor Laboratory, the Broad Institute, and the Massachusetts Institute of Technology used small RNA sequencing to study the repertoire of Piwi-interacting RNAs passed from Drosophila mothers to their embryos. The work, published in this week’s issue of Science, suggests piRNAs that regulate and suppress groups of transposons called P-elements and I-elements are maternally inherited.
“This is a whole new way in which heredity can be transmitted,” senior author Gregory Hannon, a Cold Spring Harbor researcher, said in a statement. “With this finding we’ve effectively doubled the number of mechanisms by which epigenetic information is known to be inherited.”
In Drosophila, piRNAs and Piwi-interacting proteins function in what Hannon and his co-authors refer to as a “small RNA-based immune system” in germ cells. This system controls mobile DNA elements such as transposons that jump from one part of the genome to the other causing mutations and defects in the production of viable sex cells.
Proteins such as Piwi and Aubergine can pair up with piRNAs in fruit fly sex organs to suppress transposons. But prior to the study, it was unclear how that happened — and whether piRNAs specifically inherited from the mother played a role in suppressing such transposons in fruit fly embryos.
In an effort to address such questions, the researchers looked at the small RNAs found in female Drosophila and their offspring during a process called hybrid dysgenesis, in which transposons cause sterility in the offspring of crosses between wild-caught male flies (which have P- or I-element transposons) and female lab flies (which lack the transposons). If the situation is reversed, the offspring are fertile, apparently because females pass on piRNAs or other factors in the cytoplasm to suppress transposons.
The team sequenced the 18 to 29 nucleotide RNAs in the ovaries of two groups of female fruit flies: so-called inducer strains that have I-element transposons and reactive strains lacking these I-elements. They also sequenced the small RNAs in sterile (hybrid dysgenic) embryos derived from crosses between wild-caught males and laboratory-raised females and in fertile embryos derived from crosses between wild-caught females and laboratory-raised males.
The results suggest that the small RNAs from the mother are deposited in their offspring — particularly piRNAs interacting with the Aub and Piwi proteins. In contrast, the piRNAs interacting with the AGO3 protein were less likely to exhibit maternal inheritance.
Although the ovarian transposons-targeting piRNA patterns were similar between inducer and reactive strains, reactive strains did not have as many piRNAs as inducer strains and also deposited fewer piRNAs in their embryos.
Two weeks after fertilization, though, the sterile offspring of reactive females and the fertile offspring of inducer females had more comparable piRNA profiles. Even so, the fertile offspring still had about seven times as many piRNAs directed at the I-element transposons. These piRNAs appear to help then repress paternal I-elements, whereas sterile offspring lack sufficient piRNAs to repress transposons inherited from the father.
Maternally inherited small RNAs also seems to play a role in transposon silencing in crosses between males with P-elements and lab females. Again, these crosses produce sterile offspring when mothers lack the P-elements. In contrast, mothers with the P-elements passed on P-element piRNAs to their offspring, leading to fertile offspring.
“[T]ransmission of instructive piRNA populations, shaped by both genetic and environmental factors, may provide a previously unknown mechanism for epigenetic inheritance,” Hannon and his colleagues wrote.
The result of this piRNA inheritance is an inherited immunity resembling the adaptive immune response to pathogenic bacteria and viruses, Hannon noted. “We’ve evolved ways to transmit immunity from mother to child via the secretion of antibodies,” he said. “We now have a way in which immunity (against sterility) is passed on from mother to child, in flies but possibly other organisms also, via small RNAs.”
In the future, the team plans to investigate whether piRNAs influencing other processes are passed on in the same way. And, Hannon said, it’s possible that other organisms use similar sorts of yet-undiscovered epigenetic inheritance. “Small RNAs are probably deposited in oocytes of every animal,” he said.

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