Paralogs hnRNP L and hnRNP LL exhibit overlapping but distinct RNA binding constraints.
Paralogs hnRNP L and hnRNP LL exhibit overlapping but distinct RNA binding constraints.
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DOI：
10.1371/journal.pone.0080701
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lynch KW
中科院分区：
文献类型：
--
作者：
Smith SA;Ray D;Cook KB;Mallory MJ;Hughes TR;Lynch KW
HnRNP（异质核核糖核蛋白）蛋白是一个 RNA 结合蛋白大家族，调节 RNA 加工的多个方面。有趣的是，存在几对旁系同源的 hnRNP，它们彼此表现出相似的 RNA 结合特异性，但在体内具有非冗余的功能靶标。在这项研究中，我们系统地研究了旁系同源物 hnRNP L 和 hnRNP LL 具有不同的 RNA 结合决定簇的可能性，这可能是它们缺乏功能冗余的原因。通过结合 RNAcompete 和天然凝胶分析，我们发现虽然 hnRNP L 和 hnRNP LL 均优先结合包含重复 CA 二核苷酸的序列，但这些蛋白质对 CA 间距的要求不同。具体而言，hnRNP LL 比 hnRNP L 对 CA 重复之间的两个核苷酸空间有更严格的要求，导致 hnRNP L 比 hnRNP LL 结合更混杂。重要的是，这种对 CA 二核苷酸间距的不同要求解释了先前观察到的 hnRNP L 和 LL 对 CD45 基因内突变的敏感性差异。我们认为，重叠但不同的 RNA 结合偏好（正如我们在 hnRNP L 和 hnRNP LL 中所示）在其他 hnRNP 旁系同源物中可能很常见。
HnRNP (heterogeneous nuclear ribonucleoprotein) proteins are a large family of RNA-binding proteins that regulate numerous aspects of RNA processing. Interestingly, several paralogous pairs of hnRNPs exist that exhibit similar RNA-binding specificity to one another, yet have non-redundant functional targets in vivo. In this study we systematically investigate the possibility that the paralogs hnRNP L and hnRNP LL have distinct RNA binding determinants that may underlie their lack of functional redundancy. Using a combination of RNAcompete and native gel analysis we find that while both hnRNP L and hnRNP LL preferentially bind sequences that contain repeated CA dinucleotides, these proteins differ in their requirement for the spacing of the CAs. Specifically, hnRNP LL has a more stringent requirement for a two nucleotide space between CA repeats than does hnRNP L, resulting in hnRNP L binding more promiscuously than does hnRNP LL. Importantly, this differential requirement for the spacing of CA dinucleotides explains the previously observed differences in the sensitivity of hnRNP L and LL to mutations within the CD45 gene. We suggest that overlapping but divergent RNA-binding preferences, as we show here for hnRNP L and hnRNP LL, may be commonplace among other hnRNP paralogs.
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