A1 Refereed original research article in a scientific journal
Exonuclease Domain-Containing 1 Enhances MIWI2 piRNA Biogenesis via Its Interaction with TDRD12
Authors: Radha Raman Pandey, David Homolka, Opeyemi Olotu, Ravi Sachidanandam, Noora Kotaja, Ramesh S.Pillai
Publication year: 2018
Journal: Cell Reports
Journal name in source: Cell reports
Journal acronym: Cell Rep
Volume: 24
Issue: 13
First page : 3423
Last page: 3432.e4
Number of pages: 14
ISSN: 2211-1247
DOI: https://doi.org/10.1016/j.celrep.2018.08.087
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/35767861
PIWI proteins and their associated small RNAs,
called PIWI-interacting RNAs (piRNAs), restrict
transposon activity in animal gonads to ensure
fertility. Distinct biogenesis pathways load piRNAs
into the PIWI proteins MILI and MIWI2 in the mouse
male embryonic germline. While most MILI piRNAs
are derived via a slicer-independent pathway, MILI
slicing loads MIWI2 with a series of phased piRNAs.
Tudor domain-containing 12 (TDRD12) and its interaction
partner Exonuclease domain-containing 1
(EXD1) are required for loading MIWI2, but only
Tdrd12 is essential for fertility, leaving us with no
explanation for the physiological role of Exd1. Using
an artificial piRNA precursor, we demonstrate that
MILI-triggered piRNA biogenesis is greatly reduced
in the Exd1 mutant. The situation deteriorates in the
sensitized Exd1 mutant (Exd1/;Tdrd12+/), where
diminished MIWI2 piRNA levels de-repress LINE1
retrotransposons, leading to infertility. Thus, EXD1
enhances MIWI2 piRNA biogenesis via a functional
interaction with TDRD12.
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