Comprehensive characterization of transcript diversity at the human NODAL locus

Abstract

NODAL, a morphogen belonging to the transforming growth factor beta (TG{beta}) superfamily, is essential during embryogenesis where it induces axis formation and left-right asymmetry. NODAL is also required for the maintenance of human embryonic stem cell pluripotency, and emerges in many cancer types concomitant with metastasis and therapy resistance. Several enhancer elements have been shown to regulate mouse Nodal expression and studies have delineated mechanisms by which mRNA splicing and translation of NODAL homologues are regulated in model organisms. However, little is known regarding the co-transcriptional and post-transcriptional processing of human NODAL. Herein, we describe hitherto unreported RNAs which are transcribed from the NODAL locus, including an antisense transcript, a circular transcript, and multiple splice variants. These transcripts demonstrate the complexity of NODAL expression and highlight the need to consider each NODAL variant when attempting to quantify or target this morphogen.