Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA.
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23284, USA.
J Mol Biol. 2021 Oct 15;433(21):167229. doi: 10.1016/j.jmb.2021.167229. Epub 2021 Sep 3.
Although RNA-binding proteins (RBPs) are known to be enriched in intrinsic disorder, no previous analysis focused on RBPs interacting with specific RNA types. We fill this gap with a comprehensive analysis of the putative disorder in RBPs binding to six common RNA types: messenger RNA (mRNA), transfer RNA (tRNA), small nuclear RNA (snRNA), non-coding RNA (ncRNA), ribosomal RNA (rRNA), and internal ribosome RNA (irRNA). We also analyze the amount of putative intrinsic disorder in the RNA-binding domains (RBDs) and non-RNA-binding-domain regions (non-RBD regions). Consistent with previous studies, we show that in comparison with human proteome, RBPs are significantly enriched in disorder. However, closer examination finds significant enrichment in predicted disorder for the mRNA-, rRNA- and snRNA-binding proteins, while the proteins that interact with ncRNA and irRNA are not enriched in disorder, and the tRNA-binding proteins are significantly depleted in disorder. We show a consistent pattern of significant disorder enrichment in the non-RBD regions coupled with low levels of disorder in RBDs, which suggests that disorder is relatively rarely utilized in the RNA-binding regions. Our analysis of the non-RBD regions suggests that disorder harbors posttranslational modification sites and is involved in the putative interactions with DNA. Importantly, we utilize experimental data from DisProt and independent data from Pfam to validate the above observations that rely on the disorder predictions. This study provides new insights into the distribution of disorder across proteins that bind different RNA types and the functional role of disorder in the regions where it is enriched.
虽然已知 RNA 结合蛋白 (RBP) 富含固有无序性，但以前没有分析专门针对与特定 RNA 类型相互作用的 RBP。我们通过对与六种常见 RNA 类型（信使 RNA (mRNA)、转移 RNA (tRNA)、小核 RNA (snRNA)、非编码 RNA (ncRNA)、核糖体 RNA (rRNA) 和内部核糖体 RNA (irRNA)）结合的 RBP 中的假定无序性进行全面分析来填补这一空白。我们还分析了 RNA 结合域 (RBD) 和非 RNA 结合域区域 (non-RBD 区域) 中的假定固有无序量。与以前的研究一致，我们表明与人类蛋白质组相比，RBP 在无序性方面明显丰富。然而，更仔细的检查发现，在预测的无序性方面，mRNA、rRNA 和 snRNA 结合蛋白明显富集，而与 ncRNA 和 irRNA 相互作用的蛋白质则没有无序性富集，tRNA 结合蛋白则明显缺乏无序性。我们显示出与非 RBD 区域相关的一致性模式，即无序性富集与 RBD 中无序性水平低相关，这表明无序性在 RNA 结合区域中相对较少被利用。我们对非 RBD 区域的分析表明，无序性包含翻译后修饰位点，并参与与 DNA 的假定相互作用。重要的是，我们利用 DisProt 的实验数据和 Pfam 的独立数据来验证依赖于无序预测的上述观察结果。这项研究为结合不同 RNA 类型的蛋白质中无序性的分布以及无序性在富含无序性区域的功能作用提供了新的见解。
