Preterm birth affects over 12% of all infants born in the United States; yet the biology of early delivery remains unclear, including whether epigenetic mechanisms are involved. We examined associations of maternal and umbilical cord blood long interspersed nuclear element-1 (LINE-1) DNA methylation with length of gestation and odds of preterm birth in singleton pregnancies in Project Viva. In white blood cells from maternal blood during first trimester (n = 914) and second trimester (n = 922), and from venous cord blood at delivery (n = 557), we measured LINE-1 by pyrosequencing [expressed as %5 methyl cytosines within the LINE-1 region analyzed (%5mC)]. We ran linear regression models to analyze differences in gestation length, and logistic models for odds of preterm birth (<37 v. ⩾37 weeks’ gestation), across quartiles of LINE-1. Mean (s.d.) LINE-1 levels were 84.3 (0.6), 84.5 (0.4) and 84.6 (0.7) %5mC for first trimester, second trimester and cord blood, respectively. Mean (s.d.) gestational age was 39.5 (1.8) weeks, and 6.5% of infants were born preterm. After adjustment for maternal age, race/ethnicity, body mass index, education, smoking status and fetal sex, women with the highest v. lowest quartile of first trimester LINE-1 had longer gestations [0.45 weeks (95% CI 0.12, 0.78)] and lower odds of preterm birth [OR 0.40 (0.17, 0.94)], whereas associations with cord blood LINE-1 were in the opposite direction (−0.45 weeks, −0.83, −0.08) and [OR 4.55 (1.18, 17.5)]. In conclusion, higher early pregnancy LINE-1 predicts lower risk of preterm birth. In contrast, preterm birth is associated with lower LINE-1 in cord blood.

Export of unspliced mRNA to the cytoplasm is required for the replication of all retroviruses. In simian type D retroviruses, the RNA export is mediated by the constitutive transport element (CTE) that binds the cellular nuclear export factor 1, NXF1(TAP). To search for potential cellular RNA substrates for NXF1, we have set up an in vitro selection procedure, using an RNA library expressed from total human genomic DNA. A sequence that was isolated most frequently as independent clones exhibits extensive homology to the 3′ untranslated region of expressed LINE1 (L1) retrotransposons. This region, termed L1-NXF1 binding element (L1-NBE) bears no structural resemblance to the viral CTE, but binds NXF1 as strongly as CTE, based on gel mobility shift competition assays. A deletion analysis of the NXF1 protein reveals that CTE and L1-NBE have different, but overlapping, binding domains on NXF1. Placed in an intron, L1-NBE is capable of mediating nuclear export of lariat RNA species in Xenopus laevis oocytes and of an unspliced HIV-1 derived RNA in human 293 cells, suggesting that it may function as a nuclear export element for the intronless L1 mRNA.