Details

Autor(en) / Beteiligte

• Placentino, Maria
• de Jesus Domingues, António Miguel
• Schreier, Jan
• Dietz, Sabrina
• Hellmann, Svenja
• de Albuquerque, Bruno FM
• Butter, Falk
• Ketting, René F

Titel

Intrinsically disordered protein PID‐2 modulates Z granules and is required for heritable piRNA‐induced silencing in the Caenorhabditis elegans embryo

Ist Teil von

• The EMBO journal, 2021-02, Vol.40 (3), p.e105280-n/a

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2021

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• In Caenorhabditis elegans , the piRNA (21U RNA) pathway is required to establish proper gene regulation and an immortal germline. To achieve this, PRG‐1‐bound 21U RNAs trigger silencing mechanisms mediated by RNA‐dependent RNA polymerase (RdRP)‐synthetized 22G RNAs. This silencing can become PRG‐1‐independent and heritable over many generations, a state termed RNA‐induced epigenetic gene silencing (RNAe). How and when RNAe is established, and how it is maintained, is not known. We show that maternally provided 21U RNAs can be sufficient for triggering RNAe in embryos. Additionally, we identify PID‐2, a protein containing intrinsically disordered regions (IDRs), as a factor required for establishing and maintaining RNAe. PID‐2 interacts with two newly identified and partially redundant eTudor domain‐containing proteins, PID‐4 and PID‐5. PID‐5 has an additional domain related to the X‐prolyl aminopeptidase APP‐1, and binds APP‐1, implicating potential N‐terminal proteolysis in RNAe. All three proteins are required for germline immortality, localize to perinuclear foci, affect size and appearance of RNA inheritance‐linked Z granules, and are required for balancing of 22G RNA populations. Overall, our study identifies three new proteins with crucial functions in C. elegans small RNA silencing. SYNOPSIS Caenorhabditis elegans maternal piRNAs are sufficient to establish and maintain stable epigenetic silencing without further piRNA production (termed RNAe). Here, PID‐2 and its newly‐found interactors PID‐4 and PID‐5, are shown to be required for this heritable silencing, in addition to affecting Z granule homeostasis. Maternal piRNAs are sufficient to trigger long‐term multigenerational silencing in embryos. Intrinsically‐disordered protein PID‐2 is required for effective piRNA‐induced silencing, and interacts with Tudor‐domain proteins PID‐4 and PID‐5. PID‐2, PID‐4 and PID‐5 are required for efficient inheritance of silencing and maintenance of germline function/germline immortality across generations. PID‐2, PID‐4 and PID‐5 localize to perinuclear foci and modulate size and appearance of RNA inheritance‐linked Z granules, balancing 22G RNA populations. Graphical Abstract PID‐2 and its newly‐identified interactors PID‐4 and PID‐5 modulate size and appearance of Z granules to establish and maintain stable heritable silencing (RNAe) by maternal piRNAs.