region (UTR); heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1); pteroylglutamate (PteGlu); Dulbecco's PBS (D-PBS); chloramphenicol acetyltransferase (CAT); with a cis-element (+cis); lacking a cis-element (-cis).

Maternal folate deficiency results in selective upregulation of FR and hnRNP-E1 associated with multiple aberrations in fetal tissues that include increased cell loss, architectural anomalies, and premature differentiation. The potential significance of these findings to explain the wide spectrum of folate-responsive birth defects in humans is discussed.

Background: How do cells sense folate deficiency and then somehow restore folate homeostasis? Results: Accumulated intracellular homocysteine covalently binds heterogeneous nuclear ribonucleoprotein-E1 (hnRNP-E1) to open its high affinity mRNA-binding site and accommodate folate receptor (FR) mRNA; this triggers up-regulation of FR. Conclusion: hnRNP-E1 fulfills criteria as a cellular sensor of physiological folate deficiency. Significance: (Homocysteinylated) hnRNP-E1 also orchestrates a nutrition-sensitive posttranscriptional RNA operon during folate deficiency.

region (UTR); heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1); pteroylglutamate (PteGlu); Dulbecco's PBS (D-PBS); chloramphenicol acetyltransferase (CAT); with a cis-element (+cis); lacking a cis-element (-cis).

Background: Homocysteinylated heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) orchestrates a posttranscriptional RNA operon during folate deficiency. Results: Folate deficiency induced homocysteinylated hnRNP-E1 to bind HPV16 RNA, reduced both viral capsid proteins, promoted HPV16 DNA integration into genomic DNA, and rapidly transformed HPV16-organotypic rafts implanted in immunodeficient mice to cancer. Conclusion: A likely molecular link between folate nutrition and HPV16 is established. Significance: Folate/vitamin-B 12 deficiency can promote HPV16 DNA integration and carcinogenesis.