Alternative mRNA splicing is a fundamental process to increase the versatility of the genome. In humans, cardiac mRNA splicing is involved in the pathophysiology of heart failure. Mutations in the splicing factor RNA binding motif protein 20 (RBM20) cause severe forms of cardiomyopathy. To identify novel cardiomyopathy-associated splicing factors, RNA-seq and tissue-enrichment analyses were performed, which identified up-regulated expression of Sam68-Like mammalian protein 2 (SLM2) in the left ventricle of dilated cardiomyopathy (DCM) patients. In the human heart, SLM2 binds to important transcripts of sarcomere constituents, such as those encoding myosin light chain 2 (MYL2), troponin I3 (TNNI3), troponin T2 (TNNT2), tropomyosin 1/2 (TPM1/2), and titin (TTN). Mechanistically, SLM2 mediates intron retention, prevents exon exclusion, and thereby mediates alternative splicing of the mRNA regions encoding the variable proline-, glutamate-, valine-, and lysine-rich (PEVK) domain and another part of the I-band region of titin. In summary, SLM2 is a novel cardiac splicing regulator with essential functions for maintaining cardiomyocyte integrity by binding to and processing the mRNAs of essential cardiac constituents such as titin.

选择性 mRNA剪接是增加基因组多功能性的基本过程。在人类中，心脏 mRNA 剪接参与心力衰竭的病理生理学。剪接因子 RNA 结合基序蛋白 20 (RBM20) 的突变会导致严重的心肌病。为了鉴定新的心肌病相关剪接因子，进行了 RNA-seq 和组织富集分析，确定了扩张型心肌病 ( DCM ) 患者左心室中Sam68 样哺乳动物蛋白 2 ( SLM2 ) 的上调表达。在人类心脏中，SLM2 与肌节成分的重要转录物结合，例如编码肌球蛋白轻链 2 ( MYL2 )、肌钙蛋白 I3 ( TNNI3 ))、肌钙蛋白 T2 ( TNNT2 )、原肌球蛋白 1/2 ( TPM1/2 ) 和肌动蛋白( TTN )。从机制上讲，SLM2 介导内含子保留，防止外显子排斥，从而介导编码可变脯氨酸、谷氨酸、缬氨酸和富含赖氨酸 (PEVK) 结构域的 mRNA 区域和 I 带区域的另一部分的可变剪接。提丁。总之，SLM2 是一种新型心脏剪接调节剂，具有通过结合和处理基本心脏成分（如肌动蛋白）的 mRNA 来维持心肌细胞完整性的基本功能。