Center for Genomics & Systems Biology, Department of Biology, New York University, New York, NY, 10012, USA.
Center for Genomics & Systems Biology, NYU Abu Dhabi, P.O. Box 129188, Saadiyat Island, Abu Dhabi, United Arab Emirates.
Genome Biol. 2018 Jan 24;19(1):8. doi: 10.1186/s13059-017-1369-x.
The 3' untranslated regions (UTRs) of mRNAs play a major role in post-transcriptional regulation of gene expression. Selection of transcript cleavage and polyadenylation sites is a dynamic process that produces multiple transcript isoforms for the same gene within and across different cell types. Using LITE-Seq, a new quantitative method to capture transcript 3' ends expressed in vivo, we have characterized sex- and cell type-specific transcriptome-wide changes in gene expression and 3'UTR diversity in Caenorhabditis elegans germline cells undergoing proliferation and differentiation.
We show that nearly half of germline transcripts are alternatively polyadenylated, that differential regulation of endogenous 3'UTR variants is common, and that alternative isoforms direct distinct spatiotemporal protein expression patterns in vivo. Dynamic expression profiling also reveals temporal regulation of X-linked gene expression, selective stabilization of transcripts, and strong evidence for a novel developmental program that promotes nucleolar dissolution in oocytes. We show that the RNA-binding protein NCL-1/Brat is a posttranscriptional regulator of numerous ribosome-related transcripts that acts through specific U-rich binding motifs to down-regulate mRNAs encoding ribosomal protein subunits, rRNA processing factors, and tRNA synthetases.
These results highlight the pervasive nature and functional potential of patterned gene and isoform expression during early animal development.
mRNA 的 3'非翻译区 (UTR) 在基因表达的转录后调控中起着主要作用。转录本切割和多聚腺苷酸化位点的选择是一个动态过程,它在同一基因内和不同细胞类型之间产生多个转录本异构体。我们使用 LITE-Seq,一种新的定量方法来捕获体内表达的转录本 3'末端,对性和细胞类型特异性的生殖细胞中基因表达和 3'UTR 多样性进行了全转录组范围的研究,这些细胞经历了增殖和分化。
我们表明,近一半的生殖细胞转录本是可变多聚腺苷酸化的,内源性 3'UTR 变体的差异调节是常见的,并且替代的同工型在体内指导不同的时空蛋白质表达模式。动态表达谱分析还揭示了 X 连锁基因表达的时间调节、转录本的选择性稳定,以及强烈证据表明存在一种新的发育程序,该程序促进卵母细胞中核仁溶解。我们表明,RNA 结合蛋白 NCL-1/Brat 是许多与核糖体相关的转录本的转录后调节剂,它通过特定的 U 丰富结合基序发挥作用,下调编码核糖体蛋白亚基、rRNA 加工因子和 tRNA 合成酶的 mRNA。
这些结果突出了早期动物发育过程中模式化基因和同工型表达的普遍性质和功能潜力。