STUB1 polyadenylation signal variant AACAAA does not affect polyadenylation but decreases STUB1 translation causing SCAR16
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Tarih
2018
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
John Wiley and Sons Inc.
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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.
Açıklama
Anahtar Kelimeler
3?UTR, cerebellar atrophy, polyadenylation, SCAR16, STUB1
Kaynak
Human Mutation
WoS Q Değeri
Scopus Q Değeri
Q1
Cilt
39
Sayı
10
