Conboy J
Life Sciences Division, Lawrence Berkeley Laboratory, University of California, Berkeley 94720, USA.
Proc Soc Exp Biol Med. 1999 Feb;220(2):73-8. doi: 10.1046/j.1525-1373.1999.d01-12.x.
Alternative pre-mRNA splicing plays a major role in regulating cell type-specific expression of the protein 4.1 family of skeletal proteins. The biological importance of alternative splicing as a mechanism for 4.1 gene regulation is underscored by studies of the prototypical 4.1R gene in erythroid cells: activation of exon 16 inclusion in mRna at the erythroblast stage greatly enhances the ability of newly synthesized 4.1R protein to bind spectrin and actin, and thus assemble into a stable membrane skeleton. This gain-of- function has profound effects on the biophysical properties of deformability and membrane strength that are critical to red cell survival in the circulation. Another example of developmentally regulated splicing occurs in differentiating mammary epithelial cells in culture, where cell morphogenesis is accompanied by a splicing switch that reversibly activates inclusion of alternative exon muscle. Few other genes are known to be so richly endowed with regulated switches in pre-mRna splicing making the 4.1R gene an interesting paradigm for the role of alternative splicing as a mediator of cell function. Recent evidence that other members of the 4.1 gene family are also regulated by alternative splicing suggests, moreover, that this phenomenon is of general importance in regulating the structure of this class of skeletal proteins.
可变前体mRNA剪接在调节骨骼蛋白4.1家族蛋白的细胞类型特异性表达中起主要作用。对红细胞中典型的4.1R基因的研究强调了可变剪接作为4.1基因调节机制的生物学重要性：在成红细胞阶段，mRNA中外显子16的包含激活大大增强了新合成的4.1R蛋白结合血影蛋白和肌动蛋白的能力，从而组装成稳定的膜骨架。这种功能获得对变形性和膜强度的生物物理特性有深远影响，而这些特性对于循环中红细胞的存活至关重要。另一个发育调控剪接的例子发生在培养中的分化乳腺上皮细胞中，细胞形态发生伴随着剪接开关，该开关可逆地激活可变外显子肌肉的包含。已知很少有其他基因在前体mRNA剪接中具有如此丰富的调控开关，这使得4.1R基因成为可变剪接作为细胞功能调节因子作用的一个有趣范例。此外，最近的证据表明4.1基因家族的其他成员也受可变剪接调控，这表明这种现象在调节这类骨骼蛋白的结构中具有普遍重要性。
