SRSF1, a member of the SR protein family, is an important splicing factor and regulator of splicing. Multiple splicing isoforms have been reported for this gene. SRSF1-3, a splicing isoform of SRSF1, is necessary for AID-dependent SHM of IgV genes. However, its precise role in SHM remains enigmatic. Transcriptomic analysis of SRSF1-3 reconstituted cells shows upregulation of transcription factor SATB2 and chromatin regulator UBN1. The increased SATB2 and UBN1 are strikingly enriched in the MAR and promoter regions of the IgL gene, respectively. Furthermore, UBN1 enrichment at the promoter region was coupled with a hundred-fold enhanced occupancy of the histone variant H3.3 at the IgL promoter, that is a hallmark of efficient SHM. The enhanced occupancy of SATB2 at the MAR, UBN1 and histone variant H3.3 at the IgL promoter leads to an increase in IgL transcription, revealing a role of SRSF1-3 in SHM. Thus, SRSF1-3 is likely involved in the regulation of SHM, via upregulation of a crucial transcription factor SATB2, as well as, by overexpression of a chromatin modulator of Ig genes, UBN1, which further assists in the recruitment of the histone variant H3.3. Furthermore, the splicing isoform SRSF1-3 regulates alternate splicing pattern of splicing isoforms for various crucial genes. The present study provides the first evidence that a splicing isoform of an SR protein can regulate the post-transcriptional processing of RNA in vivo.

中文翻译：

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SRSF1-3是一种剪接和体细胞超突变调节剂，它通过染色质调节剂SATB2，UBN1和组蛋白变体H3.3控制IgV基因的转录。

SRSF1是SR蛋白家族的成员，是重要的剪接因子和剪接调节剂。已经报道了该基因的多个剪接同工型。SRSF1-3，SRSF1的剪接同工型，对于IgV基因的AID依赖性SHM是必需的。但是，它在SHM中的确切作用仍然是个谜。SRSF1-3重构细胞的转录组学分析显示转录因子SATB2和染色质调节剂UBN1上调。增加的SATB2和UBN1分别显着富集在IgL基因的MAR和启动子区域。此外，UBN1在启动子区域的富集与组蛋白变体H3.3在IgL启动子上的占有率提高了一百倍，这是有效SHM的标志。SATB2在MAR，UBN1和组蛋白变体H3中的占用增加。IgL启动子上的3导致IgL转录增加，从而揭示SRSF1-3在SHM中的作用。因此，SRSF1-3可能通过重要转录因子SATB2的上调，以及过表达Ig基因的染色质调节剂UBN1来参与SHM的调节，这进一步有助于募集组蛋白变异体H3 .3。此外，剪接同工型SRSF1-3调节各种关键基因的剪接同工型的交替剪接模式。本研究提供了第一个证据，即SR蛋白的剪接同工型可以调节体内RNA的转录后加工。Ig基因的染色质调节剂UBN1的过表达，进一步协助了组蛋白变体H3.3的募集。此外，剪接同工型SRSF1-3调节各种关键基因的剪接同工型的交替剪接模式。本研究提供了第一个证据，即SR蛋白的剪接同工型可以调节体内RNA的转录后加工。Ig基因的染色质调节剂UBN1的过表达，进一步协助了组蛋白变体H3.3的募集。此外，剪接同工型SRSF1-3调节各种关键基因的剪接同工型的替代剪接模式。本研究提供了第一个证据，即SR蛋白的剪接同工型可以调节体内RNA的转录后加工。