Mice deficient in oocyte-specific oligoadenylate synthetase-like protein OAS1D display reduced fertility.
The double-stranded RNA (dsRNA)-induced interferon response is a defense mechanism against viral infection. Upon interferon activation by dsRNA, 2',5'-oligoadenylate synthetase 1 (OAS1A) is induced; it binds dsRNA and converts ATP into 2',5'-linked oligomers of adenosine (called 2-5A), which activate RNase L that in turn degrades viral and cellular RNAs. In a screen to identify oocyte-specific genes, we identified a novel murine cDNA encoding an ovary-specific 2',5'-oligoadenylate synthetase-like protein, OAS1D, which displays 59% identity with OAS1A. OAS1D is predominantly cytoplasmic and is exclusively expressed in growing oocytes and early embryos. Like OAS1A, OAS1D binds the dsRNA mimetic poly(I-C), but unlike OAS1A, it lacks 2'-5' adenosine linking activity. OAS1D interacts with OAS1A and inhibits the enzymatic activity of OAS1A. Mutant mice lacking OAS1D (Oas1d(-/-)) display reduced fertility due to defects in ovarian follicle development, decreased efficiency of ovulation, and eggs that are fertilized arrest at the one-cell stage. These effects are exacerbated after activation of the interferon/OAS1A/RNase L pathway by poly(I-C). We propose that OAS1D suppresses the interferon/OAS/RNase L-mediated cellular destruction by interacting with OAS1A during oogenesis and early embryonic development.
Yan
Wei
W
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Ma
Lang
L
Stein
Paula
P
Pangas
Stephanie A
SA
Burns
Kathleen H
KH
Bai
Yuchen
Y
Schultz
Richard M
RM
Matzuk
Martin M
MM
D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D003593:Cytoplasm / Q000737:chemistry / Q000201:enzymology; D047108:Embryonic Development; D005260:Female; D015870:Gene Expression; D007247:Infertility, Female / Q000201:enzymology*; D007369:Interferon Inducers / Q000494:pharmacology; D007372:Interferons / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D010060:Ovulation; D011070:Poly I-C / Q000494:pharmacology; D014176:Protein Biosynthesis; D012330:RNA, Double-Stranded / Q000378:metabolism
D007369:Interferon Inducers; D012330:RNA, Double-Stranded; D007372:Interferons; C502208:Oas1d protein, mouse; D015088:2',5'-Oligoadenylate Synthetase; D011070:Poly I-C