Department of Biochemistry and Molecular Pharmacology, 364 Plantation Street, LRB-906, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20252-7. doi: 10.1073/pnas.0907916106. Epub 2009 Nov 13.
Totipotent stem cells have the potential to differentiate into every cell type. Renewal of totipotent stem cells in the germline and cellular differentiation during early embryogenesis rely upon posttranscriptional regulatory mechanisms. The Caenorhabditis elegans RNA binding protein, MEX-3, plays a key role in both processes. MEX-3 is a maternally-supplied factor that controls the RNA metabolism of transcripts encoding critical cell fate determinants. However, the nucleotide sequence specificity and requirements of MEX-3 mRNA recognition remain unclear. Only a few candidate regulatory targets have been identified, and the full extent of the network of MEX-3 targets is not known. Here, we define the consensus sequence required for MEX-3 RNA recognition and demonstrate that this element is required for MEX-3 dependent regulation of gene expression in live worms. Based on this work, we identify several candidate MEX-3 targets that help explain its dual role in regulating germline stem cell totipotency and embryonic cell fate specification.
全能干细胞具有分化为每种细胞类型的潜力。生殖细胞中全能干细胞的更新和早期胚胎发生过程中的细胞分化依赖于转录后调控机制。秀丽隐杆线虫的 RNA 结合蛋白 MEX-3 在这两个过程中都起着关键作用。MEX-3 是一种母源提供的因子,控制着编码关键细胞命运决定因素的转录本的 RNA 代谢。然而,MEX-3 mRNA 识别的核苷酸序列特异性和要求仍不清楚。仅鉴定了少数几个候选调控靶标,并且不知道 MEX-3 靶标的完整网络。在这里,我们定义了 MEX-3 RNA 识别所需的共识序列,并证明该元件对于 MEX-3 依赖的活体蠕虫中基因表达的调控是必需的。基于这项工作,我们确定了几个候选的 MEX-3 靶标,这有助于解释其在调节生殖细胞干细胞全能性和胚胎细胞命运特化方面的双重作用。