Farah Alul and Ji Wan will present their research on Thursday 23rd August 2012
Farah’s Research Summary
Genetics of Thyroid Stimulating Hormone Variability in Newborns
In the United States, the overall infant mortality rate was estimated in 2006 at about 6.68 per 1,000 live births. Preterm infants have the largest impact on overall US infant mortality, followed by congenital malformations. Part of the congenital malformations are congenital endocrine disorders, of these, congenital hypothyroidism (CH) is the most common. CH is one of the disorders screened for in the newborn screening program and is detected through measuring thyroxine (T4) and thyroid stimulating hormone (TSH) levels. A major contributor to false results in CH screening is the high variability of TSH level in healthy newborns. Therefore, a better understanding of the normal variation in TSH, particularly in preterm infants, may improve the sensitivity of its use in newborn screening as well as provide a better understanding of the thyroid profile and disorders in newborns and premature infants. In this project, we aim to determine the heritability of TSH variation in newborns as well as identify SNPs associated with the normal variation in TSH levels in euthyroid preterm and term infants.
Ji’s Research Summary
Genome-wide analysis of direct RNA sequencing data reveals a role of polyC binding proteins in the regulation of mRNA stability and alternative polyadenylation
The KH-domain protein aCP was previously demonstrated to bind to the 3’ UTR of the nascent ha-globin transcript affecting the efficiency of 3’ processing in the nucleus and mRNA stability in the cytoplasm. We assessed the genome-wide impact of aCP RNP complexes on 3’ processing with specific focus on its impact on mRNA stability and alternative polyA site utilization (APA). The major isoforms of aCP were acutely depleted from a human hematopoetic cell line (K562) and the impact on mRNA expression and polyA site utilization was evaluated by direct RNA sequencing (DRS). Computational analysis of the DRS data revealed 586 significantly changed genes and 357 significant APA events that could be specifically linked to the aCP depletion. These events correlated strongly with the presence of C-rich sequences in close proximity to the impacted polyA sites. The most prominent association was the presence of a C-rich motif within a window 30-40 bases 5’ to polyA signals (AAUAAA). These findings predict a role of aCPs in controlling post-transcriptional pathways as the upstream enhance (USE) in the 3’ UTRs of human transcriptome.