The placenta supports many physiological functions for the developing fetus. Abnormality of placenta is the major cause of infertility and gestational complications. Trophoblast differentiation is a key component of placenta development. Cleavage/polyadenylation (C/P) of nascent transcript is an essential processing step for most eukaryotic mRNAs and is coupled to termination of transcription. Genomic studies in the past few years have revealed that most mammalian genes have multiple C/P sites (pAs), resulting in alternative cleavage and polyadenylation (APA) isoforms. APA is rapidly recognized as an important layer of gene regulation, impacting protein diversity and mRNA metabolism. Our lab has previously found that promoter-distal pAs are preferentially used during cell differentiation and development compared to promoter-proximal ones. However, we recently found that, to our surprise, in vitro models for trophoblast differentiation involve substantial activation of promote-proximal pAs, leading to shortening of 3'UTRs. In this project, we plan to explore this novel finding with physiologically relevant in vivo samples and examine the consequences of global APA regulation for mRNA metabolism in trophoblast cells.
The placenta supports many physiological functions for the developing fetus. Abnormality of placenta is the major cause of infertility and gestational complications. Trophoblast differentiation is a key component of placenta development. We recently found that, to our surprise, differentiation of trophoblast cells using in vitro models involves substantial activation of promoter-proximal cleavage/polyadenylation sites, leading to shortening of 3'UTRs. In this project, we plan to explore this novel finding with physiologically relevant in vivo samples and examine the consequences of global APA regulation for mRNA metabolism in trophoblast cells.
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| Skamagki, Maria; Correia, Cristina; Yeung, Percy et al. (2017) ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors. Nat Cell Biol 19:1037-1048 |
