Pagano Daniel J, Kingston Elena R, Kim Dennis H
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
PLoS Genet. 2015 Feb 11;11(2):e1004997. doi: 10.1371/journal.pgen.1004997. eCollection 2015 Feb.
Analyses of gene expression profiles in evolutionarily diverse organisms have revealed a role for microRNAs in tuning tissue-specific gene expression. Here, we show that the relatively abundant and constitutively expressed miR-58 family of microRNAs sharply defines the tissue-specific expression of the broadly transcribed gene encoding PMK-2 p38 MAPK in Caenorhabditis elegans. Whereas PMK-2 functions redundantly with PMK-1 in the nervous system to regulate neuronal development and behavioral responses to pathogenic bacteria, the miR-58, miR-80, miR-81, and miR-82 microRNAs function redundantly to destabilize pmk-2 mRNA in non-neuronal cells with switch-like potency. Our data suggest a role for the miR-58 family in the establishment of neuronal-specific gene expression in C. elegans, and support a more general role for microRNAs in the establishment of tissue-specific gene expression.
对进化上不同生物的基因表达谱分析揭示了微小RNA在调节组织特异性基因表达中的作用。在此,我们表明线虫中相对丰富且组成性表达的微小RNA miR-58家族明确界定了广泛转录的编码PMK-2 p38丝裂原活化蛋白激酶基因的组织特异性表达。虽然PMK-2在神经系统中与PMK-1冗余发挥作用以调节神经元发育和对病原菌的行为反应,但miR-58、miR-80、miR-81和miR-82微小RNA在非神经元细胞中以类似开关的效力冗余发挥作用使pmk-2 mRNA不稳定。我们的数据表明miR-58家族在秀丽隐杆线虫神经元特异性基因表达的建立中发挥作用,并支持微小RNA在组织特异性基因表达建立中发挥更普遍的作用。