Li Yang I, Sanchez-Pulido Luis, Haerty Wilfried, Ponting Chris P
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom;
Genome Res. 2015 Jan;25(1):1-13. doi: 10.1101/gr.181990.114.
Ninety-four percent of mammalian protein-coding exons exceed 51 nucleotides (nt) in length. The paucity of micro-exons (≤ 51 nt) suggests that their recognition and correct processing by the splicing machinery present greater challenges than for longer exons. Yet, because thousands of human genes harbor processed micro-exons, specialized mechanisms may be in place to promote their splicing. Here, we survey deep genomic data sets to define 13,085 micro-exons and to study their splicing mechanisms and molecular functions. More than 60% of annotated human micro-exons exhibit a high level of sequence conservation, an indicator of functionality. While most human micro-exons require splicing-enhancing genomic features to be processed, the splicing of hundreds of micro-exons is enhanced by the adjacent binding of splice factors in the introns of pre-messenger RNAs. Notably, splicing of a significant number of micro-exons was found to be facilitated by the binding of RBFOX proteins, which promote their inclusion in the brain, muscle, and heart. Our analyses suggest that accurate regulation of micro-exon inclusion by RBFOX proteins and PTBP1 plays an important role in the maintenance of tissue-specific protein-protein interactions.
94%的哺乳动物蛋白质编码外显子长度超过51个核苷酸（nt）。微小外显子（≤51 nt）数量稀少，这表明剪接机制对它们的识别和正确加工比对外显子更长的情况面临更大挑战。然而，由于数千个人类基因含有已加工的微小外显子，可能存在专门的机制来促进它们的剪接。在这里，我们全面分析深度基因组数据集以定义13,085个微小外显子，并研究它们的剪接机制和分子功能。超过60%的已注释人类微小外显子表现出高水平的序列保守性，这是功能的一个指标。虽然大多数人类微小外显子需要剪接增强的基因组特征才能进行加工，但数百个微小外显子的剪接通过前体信使RNA内含子中剪接因子的相邻结合而得到增强。值得注意的是，发现大量微小外显子的剪接因RBFOX蛋白的结合而得到促进，RBFOX蛋白促进它们在脑、肌肉和心脏中的包含。我们的分析表明，RBFOX蛋白和PTBP1对微小外显子包含的精确调控在维持组织特异性蛋白质-蛋白质相互作用中起重要作用。
