University of Calgary, Department of Biological Sciences, Alberta, Calgary, Canada.
Dev Dyn. 2012 Mar;241(3):505-21. doi: 10.1002/dvdy.23735. Epub 2012 Jan 30.
For a stem cell population to exist over an extended period, a balance must be maintained between self-renewing (proliferating) and differentiating daughter cells. Within the Caenorhabditis elegans germ line, this balance is controlled by a genetic regulatory pathway, which includes the canonical Notch signaling pathway.
Genetic screens identified the gene teg-1 as being involved in regulating the proliferation versus differentiation decision in the C. elegans germ line. Cloning of TEG-1 revealed that it is a homolog of mammalian CD2BP2, which has been implicated in a number of cellular processes, including in U4/U6.U5 tri-snRNP formation in the pre-mRNA splicing reaction. The position of teg-1 in the genetic pathway regulating the proliferation versus differentiation decision, its single mutant phenotype, and its enrichment in nuclei, all suggest TEG-1 also functions as a splicing factor. TEG-1, as well as its human homolog, CD2BP2, directly bind to UAF-1 U2AF65, a component of the U2 auxiliary factor.
TEG-1 functions as a splicing factor and acts to regulate the proliferation versus meiosis decision. The interaction of TEG-1 CD2BP2 with UAF-1 U2AF65, combined with its previously described function in U4/U6.U5 tri-snRNP, suggests that TEG-1 CD2BP2 functions in two distinct locations in the splicing cascade.
为了使干细胞群体能够长期存在,必须在自我更新(增殖)和分化的子细胞之间保持平衡。在秀丽隐杆线虫的生殖系中,这种平衡是由一个遗传调控途径控制的,其中包括经典的 Notch 信号通路。
遗传筛选确定了基因 teg-1 参与调节线虫生殖系中增殖与分化的决定。TEG-1 的克隆表明,它是哺乳动物 CD2BP2 的同源物,CD2BP2 已被涉及许多细胞过程,包括在 U4/U6.U5 三 snRNP 的形成中的前体 mRNA 剪接反应。teg-1 在调节增殖与分化决定的遗传途径中的位置、其单突变表型及其在核中的富集,都表明 TEG-1 也作为剪接因子发挥作用。TEG-1 及其人类同源物 CD2BP2 直接与 U2 辅助因子的组成部分 UAF-1 U2AF65 结合。
TEG-1 作为剪接因子发挥作用,调节增殖与减数分裂的决定。TEG-1 CD2BP2 与 UAF-1 U2AF65 的相互作用,结合其在 U4/U6.U5 三 snRNP 中的先前描述的功能,表明 TEG-1 CD2BP2 在剪接级联中的两个不同位置发挥作用。