The four Zn fingers of MBNL1 provide a flexible platform for recognition of its RNA binding elements.
The four Zn fingers of MBNL1 provide a flexible platform for recognition of its RNA binding elements.
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DOI：
10.1186/1471-2199-12-20
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发表时间：
2011-05-06
影响因子：
--
通讯作者：
Berglund JA
中科院分区：
文献类型：
--
作者：
Cass D;Hotchko R;Barber P;Jones K;Gates DP;Berglund JA
肌盲样蛋白1（MBNL 1）是一种含有4个CCCH锌指（ZnFs）的选择性剪接因子。通过扩增的CUG和CCUG重复序列隔离MBNL 1是引起强直性肌营养不良的主要成分。除了结合结构化扩展的CUG和CCUG重复序列之外，先前的结果表明MBNL 1结合含有GC二核苷酸的单链RNA。我们对MBNL 1与单链RNA的结合进行了系统分析。这些研究表明，多聚尿苷中的单个GC二核苷酸足以与MBNL 1结合，第二个GC二核苷酸赋予更高的MBNL 1结合亲和力。然而，额外的GC二核苷酸不增强RNA结合。我们还发现，与GC二核苷酸相邻的RNA序列在MBNL 1结合中起重要作用，具有以下偏好：尿苷>胞苷>腺苷>鸟苷。对于MBNL 1的高亲和力结合，两个GC二核苷酸之间的距离可以在1至17个核苷酸之间变化。这些结果表明，MBNL 1是高度灵活的，能够采用不同的构象，以识别具有不同序列构型的RNA。虽然MBNL 1含有四个ZnF，但只有两个ZnF-GC二核苷酸相互作用是高亲和力结合所必需的.
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. 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. 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.
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