GASZ is essential for male meiosis and suppression of retrotransposon expression in the male germline.
Nuage are amorphous ultrastructural granules in the cytoplasm of male germ cells as divergent as Drosophila, Xenopus, and Homo sapiens. Most nuage are cytoplasmic ribonucleoprotein structures implicated in diverse RNA metabolism including the regulation of PIWI-interacting RNA (piRNA) synthesis by the PIWI family (i.e., MILI, MIWI2, and MIWI). MILI is prominent in embryonic and early post-natal germ cells in nuage also called germinal granules that are often associated with mitochondria and called intermitochondrial cement. We find that GASZ (Germ cell protein with Ankyrin repeats, Sterile alpha motif, and leucine Zipper) co-localizes with MILI in intermitochondrial cement. Knockout of Gasz in mice results in a dramatic downregulation of MILI, and phenocopies the zygotene-pachytene spermatocyte block and male sterility defect observed in MILI null mice. In Gasz null testes, we observe increased hypomethylation and expression of retrotransposons similar to MILI null testes. We also find global shifts in the small RNAome, including down-regulation of repeat-associated, known, and novel piRNAs. These studies provide the first evidence for an essential structural role for GASZ in male fertility and epigenetic and post-transcriptional silencing of retrotransposons by stabilizing MILI in nuage.
Ma
Lang
L
Department of Pathology, Baylor College of Medicine, Houston, Texas, United States of America.
Buchold
Gregory M
GM
Greenbaum
Michael P
MP
Roy
Angshumoy
A
Burns
Kathleen H
KH
Zhu
Huifeng
H
Han
Derek Y
DY
Harris
R Alan
RA
Coarfa
Cristian
C
Gunaratne
Preethi H
PH
Yan
Wei
W
Matzuk
Martin M
MM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D060565:Argonaute Proteins; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018626:Retroelements; D013094:Spermatozoa / Q000166:cytology* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D060565:Argonaute Proteins; D029721:Drosophila Proteins; C583034:GASZ protein, Drosophila; C467809:Gasz protein, mouse; C448521:Piwil2 protein, mouse; D011506:Proteins; D034741:RNA, Small Interfering; D018626:Retroelements