Stub1 Polyadenylation Signal Variant Aacaaa Does Not Affect Polyadenylation But Decreases Stub1 Translation Causing Scar16

PubMed: 30058754 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. © 2018 Wiley Periodicals, Inc. Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK: 114Z829 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK Sehime G. Temel, Department of Medical Genetics, Department of Histology and Embryology, Faculty of Medicine, Uludag? University, Gorukle Campus, 16059 Nilufer, Bursa, Turkey Email: sehimegtemel@hotmail.com Aslıhan Tolun, Department of Molecular Biology andGenetics,Bog?aziçiUniversity,Istanbul, Turkey. Email: tolun@boun.edu.tr Funding Information This study was supported by the Scientific and Technological Research Council of Turkey (TÜBITAK) Grant 114Z829.