A trans-homologue interaction between reciprocally imprinted miR-127 and Rtl1 regulates placenta development
Adalsteinsson, Bjorn T
Allen, Sarah E
Stewart, Colin L
Company of Biologists
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Ito, M., Sferruzzi-Perri, A., Edwards, C., Adalsteinsson, B. T., Allen, S. E., Loo, T., Kitazawa, M., et al. (2015). A trans-homologue interaction between reciprocally imprinted miR-127 and Rtl1 regulates placenta development. Development, 142 2425-2430. https://doi.org/10.1242/dev.121996
The paternally expressed imprinted Retrotransposon-like 1 (Rtl1/Peg11) is a retrotransposon-derived gene that has evolved a function in eutherian placentation. Seven miRNAs, including miR-127, are processed from a maternally expressed antisense Rtl1 transcript (Rtl1as) and regulate Rtl1 levels through RNAi-mediated post-transcriptional degradation. To determine the relative functional role of Rtl1as miRNAs in Rtl1 dosage, we generated a mouse specifically deleted for miR-127. The miR-127 knockout mice exhibit placentomegaly with specific defects within the labyrinthine zone involved in maternal-fetal nutrient transfer. Although fetal weight is unaltered, specific Rtl1 transcripts and protein levels are increased in both the fetus and placenta. Phenotypic analysis of single (ΔmiR-127/Rtl1 or miR-127/ΔRtl1) and double (ΔmiR-127/ΔRtl1) heterozygous miR-127 and Rtl1 deficient mice indicate that Rtl1 is the main target gene of miR-127 in placental development. Our results demonstrate that miR-127 is an essential regulator of Rtl1 mediated by a trans-homologue interaction between reciprocally imprinted genes on the maternally and paternally inherited chromosomes.
Genomic imprinting, Rtl1, miR-127, placenta development
This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) and EU FP7 Marie Curie Action 290123 (INGENIUM). This work was partly funded by a National Health and Medical Research Council (NHMRC) CJ Martin Biomedical Fellowship to A.N.S.P.
Wellcome Trust (095606/Z/11/Z)
EC FP7 MC ITN (290123)
External DOI: https://doi.org/10.1242/dev.121996
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248918