Human pre-mRNA introns vary in size from under fifty to over a million nucleotides. We searched for essential factors involved in the splicing of human short introns by screening siRNAs against 154 human nuclear proteins. The splicing activity was assayed with a model HNRNPH1 pre-mRNA containing short 56-nucleotide intron. We identified a known alternative splicing regulator SPF45 (RBM17) as a constitutive splicing factor that is required to splice out this 56-nt intron. Whole-transcriptome sequencing of SPF45-deficient cells revealed that SPF45 is essential in the efficient splicing of many short introns. To initiate the spliceosome assembly on a short intron with the truncated poly-pyrimidine tract, the U2AF-homology motif (UHM) of SPF45 competes out that of U2AF65 for binding to the UHM-ligand motif (ULM) of the U2 snRNP protein SF3b155 (SF3B1). We propose that splicing in a distinct subset of human short introns depends on SPF45 but not U2AF heterodimer.

中文翻译：

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依赖于SPF45 / RBM17，但不依赖于U2AF的人类短内含子的不同子集

人类前mRNA内含子的大小从50个核苷酸到100万个核苷酸不等。我们通过针对154种人类核蛋白的siRNA筛选了与人类短内含子剪接有关的基本因子。剪接活性用包含短56个核苷酸内含子的HNRNPH1前mRNA模型进行分析。我们确定了一个已知的替代剪接调节剂SPF45（RBM17）作为组成性剪接因子，需要剪接出这个56 nt的内含子。SPF45缺陷细胞的全转录组测序表明，SPF45在许多短内含子的有效剪接中必不可少。为了在截短的聚嘧啶束短内含子上启动剪接体组装，SPF45的U2AF同源基序（UHM）竞争U2AF65的同源基序，以与U2 snRNP蛋白SF3b155的UHM配体基序（ULM）结合（ SF3B1）。