The four Zn fingers of MBNL1 provide a flexible platform for recognition of its RNA binding elements
| Autor: | Kimberly Jones, Devika P. Gates, J. Andrew Berglund, Danielle M. Cass, Paul A. Barber, Rachel Hotchko |
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| Jazyk: | angličtina |
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Models
Molecular lcsh:QH426-470 Guanine RNA-binding protein Plasma protein binding Biology Cytosine Nucleotides 03 medical and health sciences chemistry.chemical_compound Cytosine nucleotide MBNL1 Nucleotide lcsh:QH573-671 Molecular Biology 030304 developmental biology chemistry.chemical_classification Zinc finger 0303 health sciences Base Sequence lcsh:Cytology 030302 biochemistry & molecular biology RNA RNA-Binding Proteins Zinc Fingers Guanine Nucleotides lcsh:Genetics chemistry Biochemistry Research Article Protein Binding |
| Zdroj: | BMC Molecular Biology, Vol 12, Iss 1, p 20 (2011) BMC Molecular Biology |
| ISSN: | 1471-2199 |
| DOI: | 10.1186/1471-2199-12-20 |
| Popis: | Background Muscleblind-like 1 (MBNL1) is an alternative splicing factor containing four CCCH Zinc fingers (ZnFs). The sequestration of MBNL1 by expanded CUG and CCUG repeats is a major component in causing myotonic dystrophy. In addition to binding the structured expanded CUG and CCUG repeats; previous results suggested that MBNL1 binds single-stranded RNAs containing GC dinucleotides. Results We performed a systematic analysis of MBNL1 binding to single-stranded RNAs. These studies revealed that a single GC dinucleotide in poly-uridine is sufficient for MBNL1 binding and that a second GC dinucleotide confers higher affinity MBNL1 binding. However additional GC dinucleotides do not enhance RNA binding. We also showed that the RNA sequences adjacent to the GC dinucleotides play an important role in MBNL1 binding with the following preference: uridines >cytidines >adenosines >guanosines. For high affinity binding by MBNL1, the distance between the two GC dinucleotides can vary from 1 to 17 nucleotides. Conclusions These results suggest that MBNL1 is highly flexible and able to adopt different conformations to recognize RNAs with varying sequence configurations. Although MBNL1 contains four ZnFs, only two ZnF - GC dinucleotide interactions are necessary for high affinity binding. |
| Databáze: | OpenAIRE |
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