Parra Marilyn, Gee Sherry, Chan Nadine, Ryaboy Dmitriy, Dubchak Inna, Mohandas Narla, Gascard Philippe D, Conboy John G
Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Genomics. 2004 Oct;84(4):637-46. doi: 10.1016/j.ygeno.2004.06.004.
The EPB41 (protein 4.1) genes epitomize the resourcefulness of the mammalian genome to encode a complex proteome from a small number of genes. By utilizing alternative transcriptional promoters and tissue-specific alternative pre-mRNA splicing, EPB41, EPB41L2, EPB41L3, and EPB41L1 encode a diverse array of structural adapter proteins. Comparative genomic and transcript analysis of these 140- to 240-kb genes indicates several unusual features: differential evolution of highly conserved exons encoding known functional domains interspersed with unique exons whose size and sequence variations contribute substantially to intergenic diversity; alternative first exons, most of which map far upstream of the coding regions; and complex tissue-specific alternative pre-mRNA splicing that facilitates synthesis of functionally different complements of 4.1 proteins in various cells. Understanding the splicing regulatory networks that control protein 4.1 expression will be critical to a full appreciation of the many roles of 4.1 proteins in normal cell biology and their proposed roles in human cancer.
EPB41（蛋白质4.1）基因体现了哺乳动物基因组利用少量基因编码复杂蛋白质组的能力。通过利用可变转录启动子和组织特异性可变前体mRNA剪接，EPB41、EPB41L2、EPB41L3和EPB41L1编码了一系列多样的结构衔接蛋白。对这些140至240千碱基基因的比较基因组和转录分析表明了几个不寻常的特征：编码已知功能域的高度保守外显子与独特外显子的差异进化，这些独特外显子的大小和序列变异对基因间多样性有很大贡献；可变的首个外显子，其中大多数位于编码区上游很远的位置；以及复杂的组织特异性可变前体mRNA剪接现象，这有助于在各种细胞中合成功能不同的4.1蛋白互补物。了解控制蛋白质4.1表达的剪接调控网络对于全面认识4.1蛋白在正常细胞生物学中的多种作用及其在人类癌症中的假定作用至关重要。
