STUB1 polyadenylation signal variant AACAAA does not affect polyadenylation but decreases STUB1 translation causing SCAR16
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Date
2018-07-04
Authors
Türkgenç, Burcu
Şanlıdağ, Burçin
Eker, Amber
Giray, Aslı
Kütük, Özgür
Yakıcıer, Cengiz
Tolun, Aslıhan
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Abstract
We present three siblings afflicted with a disease characterized by cerebellar ataxia, cerebellar atrophy, pyramidal tract damage with increased lower limb tendon reflexes, and onset of 31 to 57 years, which is not typical for a known disease. In a region of shared homozygosity in patients, exome sequencing revealed novel homozygous c.*240T>C variant in the 3'UTR of STUB1, the gene responsible for autosomal recessive spinocerebellar ataxia 16 (SCAR16). In other genes, such an alteration of the evolutionarily highly conserved polyadenylation signal from AATAAA to AACAAA is known to highly impair polyadenylation. In contrast, RNA sequencing and quantification revealed that neither polyadenylation nor stability of STUB1 mRNA is affected. In silico analysis predicted that the secondary structure of the mRNA is altered. We propose that this change underlies the extremely low amounts of the encoded protein in patient leukocytes.
Description
Keywords
Genetics & heredity, 3 ' UTR, Cerebellar atrophy, Polyadenylation, SCAR16, STUB1, Messenger-RNA polyadenylation, Beta-globin gene, Thalassemia, Mutation, Cleavage, Sequence, Site
Citation
Türkgenç, B. vd. (2018). ''STUB1 polyadenylation signal variant AACAAA does not affect polyadenylation but decreases STUB1 translation causing SCAR16''. Human Mutation, 39(10), 1344-1348.