Expression of Concern: ADAD2 regulates heterochromatin in meiotic and post-meiotic male germ cells via translation of MDC1

Chukrallah, Lauren G; Badrinath, Aditi; Vittor, Gabrielle G; Snyder, Elizabeth M.

doi:10.1242/jcs.260435

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“…However, neither Adad1 nor Adad2 knockout impairs RNA editing in mouse testes ( Snyder et al, 2020 ). Although ADAD2 interacts with PIWI proteins (MILI and MIWI) and a piRNA pathway factor MAEL ( Castañeda et al, 2014 ; Vagin et al, 2009 ), ADAD2 does not localize on CBs but forms unique RNA granules and regulates heterochromatin in meiotic male germ cells ( Chukrallah et al, 2022 ; Snyder et al, 2020 ). In this study, we also found that ADAD2 localizes on P-bodies that overlap with RNF17 granules and the P-body localization of ADAD2 and RNF17 are interdependent.…”

Section: Introductionmentioning

confidence: 99%

ADAD2 interacts with RNF17 in P-bodies to repress the Ping-pong cycle in pachytene piRNA biogenesis

Xiong

Yin

Gui

et al. 2023

Journal of Cell Biology

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Pachytene piRNA biogenesis is a hallmark of the germline, distinct from another wave of pre-pachytene piRNA biogenesis with regard to the lack of a secondary amplification process known as the Ping-pong cycle. However, the underlying molecular mechanism and the venue for the suppression of the Ping-pong cycle remain elusive. Here, we showed that a testis-specific protein, ADAD2, interacts with a TDRD family member protein RNF17 and is associated with P-bodies. Importantly, ADAD2 directs RNF17 to repress Ping-pong activity in pachytene piRNA biogenesis. The P-body localization of RNF17 requires the intrinsically disordered domain of ADAD2. Deletion of Adad2 or Rnf17 causes the mislocalization of each other and subsequent Ping-pong activity derepression, secondary piRNAs overproduced, and disruption of P-body integrity at the meiotic stage, thereby leading to spermatogenesis arrested at the round spermatid stage. Collectively, by identifying the ADAD2-dependent mechanism, our study reveals a novel function of P-bodies in suppressing Ping-pong activity in pachytene piRNA biogenesis.

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