Conformational flexibility in the RNA stem‐loop structures formed by CAG repeats. Issue 12 (27th May 2017)

• Record Type: Journal Article
• Authors: Guo, Pei; Chan, Ho Yin Edwin; Lam, Sik Lok
• Is Part Of: FEBS letters. Volume 591:Issue 12(2017)
• Page Start: 1752
• Page End: 1760
• Publication Date: 2017-05-27
• Subjects: A·A mismatches -- CAG repeats -- loop conformational flexibility -- NMR -- RNA hairpin -- stem rigidity; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.12672
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : The expansion of CAG repeats has been found to be associated with at least nine human genetic disorders. In these disorders, the full‐length expanded CAG RNA transcripts are cleaved into small CAG‐repeated RNAs which are cytotoxic and known to be capable of forming hairpins. To better understand the RNA pathogenic mechanism, in this study we have performed high‐resolution nuclear magnetic resonance structural investigations on the RNA hairpins formed by CAG repeats. Our results show the formation of a type III AGCA tetraloop and reveal the effect of stem rigidity on the loop conformational flexibility. Abstract : Short CAG RNAs are capable of forming hairpins which cause cytotoxicity. This solution NMR study reveals the structural features of CAG hairpins. The internal dynamics of A·A mismatches affect the hairpin stem rigidity. The stem rigidity also affects the loop conformational flexibility.