title: Genome-scale microRNA and small interfering RNA screens identify small RNA modulators of TRAIL-induced apoptosis pathway.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to death receptors 4/5 and selectively induces caspase-dependent apoptosis. The RNA interference screening approach has led to the discovery and characterization of several TRAIL pathway components in human cells. Here, libraries of synthetic small interfering RNA (siRNA) and microRNAs (miRNA) were used to probe the TRAIL pathway. In addition to known genes, siRNAs targeting CDK4, PTGS1, ALG2, CLCN3, IRAK4, and MAP3K8 altered TRAIL-induced caspase-3 activation responses. Introduction of the miRNAs let-7c, mir-10a, mir-144, mir-150, mir-155, and mir-193 also affected the activation of the caspase cascade. Putative targets of these endogenous miRNAs included genes encoding death receptors, caspases, and other apoptosis-related genes. Among the novel genes revealed in the screen, CDK4 was selected for further characterization. CDK4 was the only member of the cyclin-dependent kinase gene family that bore a unique function in apoptotic signal transduction.
authors.affiliation: Asuragen Inc., Austin, Texas, USA. ovcharenko@mail.utexas.edu
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Ovcharenko
authors.forename: Kevin
authors.initials: K
authors.lastname: Kelnar
authors.forename: Charles
authors.initials: C
authors.lastname: Johnson
authors.forename: Nan
authors.initials: N
authors.lastname: Leng
authors.forename: David
authors.initials: D
authors.lastname: Brown
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D015894:Genome, Human; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D012313:RNA / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D012313:RNA; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D053148:Caspase 3; D053179:Caspase 7