Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
复制标题
DOI：
10.1016/j.cell.2016.01.029
复制
发表时间：
2016-02-11
期刊：
影响因子：
64.5
通讯作者：
Vidal M
中科院分区：
文献类型：
--
作者：
Yang X;Coulombe-Huntington J;Kang S;Sheynkman GM;Hao T;Richardson A;Sun S;Yang F;Shen YA;Murray RR;Spirohn K;Begg BE;Duran-Frigola M;MacWilliams A;Pevzner SJ;Zhong Q;Wanamaker SA;Tam S;Ghamsari L;Sahni N;Yi S;Rodriguez MD;Balcha D;Tan G;Costanzo M;Andrews B;Boone C;Zhou XJ;Salehi-Ashtiani K;Charloteaux B;Chen AA;Calderwood MA;Aloy P;Roth FP;Hill DE;Iakoucheva LM;Xia Y;Vidal M
虽然已知选择性剪接可以使某些基因的功能特征多样化，但蛋白质异构体在多大程度上对蛋白质组学规模的功能复杂性做出贡献仍是未知的。为了系统地解决这个问题，我们克隆了大量人类基因的选择性剪接转录本的全长开放阅读框架，并使用蛋白质-蛋白质相互作用图谱对数百个蛋白质异构体进行了功能比较。大多数异构体对之间的相互作用不到50%。在相互作用组网络图谱的全球背景下，不同的异构体往往表现得像不同的蛋白质，而不是彼此的微小变体。特定于替代亚型的相互作用伙伴往往以高度组织特异性的方式表达，并属于不同的功能模块。我们的策略，适用于其他功能特征，揭示了蛋白质相互作用能力通过选择性剪接的广泛扩展，并表明许多替代的‘异构体’在功能上是不同的(即‘功能异构体’)。ETOC Blurb选择性剪接的蛋白质异构体表现出显著不同的相互作用特征，因此在全球相互作用的背景下，基因组网络的行为似乎像是由不同的基因编码，而不是彼此之间的次要变体。
While alternative splicing is known to diversify the functional characteristics of some genes, the extent to which protein isoforms globally contribute to functional complexity on a proteomic scale remains unknown. To address this systematically, we cloned full-length open reading frames of alternatively spliced transcripts for a large number of human genes and used protein-protein interaction profiling to functionally compare hundreds of protein isoform pairs. The majority of isoform pairs share less than 50% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other. Interaction partners specific to alternative isoforms tend to be expressed in a highly tissue-specific manner and belong to distinct functional modules. Our strategy, applicable to other functional characteristics, reveals a widespread expansion of protein interaction capabilities through alternative splicing and suggests that many alternative ‘isoforms’ are functionally divergent (i.e., ‘functional alloforms’). eTOC Blurb Alternatively-spliced isoforms of proteins exhibit strikingly different interaction profiles and thus in the context of global interactome networks appear to behave as if encoded by distinct genes, rather than as minor variants of each other.