Nucleotide Contributions to the Structural Integrity and DNA Replication Initiation Activity of Noncoding Y RNA
| العنوان: | Nucleotide Contributions to the Structural Integrity and DNA Replication Initiation Activity of Noncoding Y RNA |
|---|---|
| المؤلفون: | Alexander R. Langley, Torsten Krude, Raphaël Rodriguez, Madzia P. Kowalski, Shang-Te Danny Hsu, Iren Wang, Shankar Balasubramanian |
| المصدر: | Biochemistry. 53:5848-5863 |
| بيانات النشر: | American Chemical Society (ACS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | DNA Replication, Genetics, Circular dichroism, Mutation, Magnetic Resonance Spectroscopy, RNA, Untranslated, DNA replication initiation, Nucleotides, Base pair, Circular Dichroism, Y RNA, Mutagenesis, DNA replication, RNA, Hydrogen Bonding, Biology, medicine.disease_cause, Biochemistry, Cell biology, Structure-Activity Relationship, medicine, Humans, Nucleic Acid Conformation, Base Pairing |
| الوصف: | Noncoding Y RNAs are small stem-loop RNAs that are involved in different cellular processes, including the regulation of DNA replication. An evolutionarily conserved small domain in the upper stem of vertebrate Y RNAs has an essential function for the initiation of chromosomal DNA replication. Here we provide a structure-function analysis of this essential RNA domain under physiological conditions. Solution state nuclear magnetic resonance and far-ultraviolet circular dichroism spectroscopy show that the upper stem domain of human Y1 RNA adopts a locally destabilized A-form helical structure involving eight Watson-Crick base pairs. Within this helix, two G:C base pairs are highly stable even at elevated temperatures and therefore may serve as clamps to maintain the local structure of the helix. These two stable G:C base pairs frame three unstable base pairs, which are located centrally between them. Systematic substitution mutagenesis results in a disruption of the ordered A-form helical structure and in the loss of DNA replication initiation activity, establishing a positive correlation between folding stability and function. Our data thus provide a structural basis for the evolutionary conservation of key nucleotides in this RNA domain that are essential for the functionality of noncoding Y RNAs during the initiation of DNA replication. |
| تدمد: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi500470b |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::268c07a59c574bcff375a597b3a98433 https://doi.org/10.1021/bi500470b |
| رقم الانضمام: | edsair.doi.dedup.....268c07a59c574bcff375a597b3a98433 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204995 00062960 |
|---|---|
| DOI: | 10.1021/bi500470b |