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Alternative mRNA Cleavage and Polyadenylation in Genetic Diseases

from SELECTBIO

The 3¹end of most transcripts is cleaved, and a stretch of adenines is added (Poly(A) tail) to allow nuclear export, stability of mature transcripts, and for efficient translation of mRNAs. 3¹end cleavage and polyadenyation of transcripts is a highly regulated process requiring several cis-acting RNA elements and more than 50 different trans-acting factors. Importantly, the majority of human genes contain alternative polyadenylation (APA) sites, indicating an important layer of gene regulation that contributes to the complexity of the transcriptome by generating isoforms that differ either in their coding or non-coding sequences. In the past two years, primarily due to the advance in transcriptome-wide 3¹end sequencing techniques, significant extensive modulation of APA was uncovered when cells were stimulated to proliferate, de-differentiate, and during cancer progression. However, factors that control APA are largely unknown. I will discuss our efforts to identify and characterize APA regulators implicated in human genetic disorder and in cancer. Exploring the role of APA has the potential to open up new avenues for a better diagnosis and therapy of cancer.

about 6 years ago

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