Biomaterial Database

A high-throughput genome-wide RNAi screen identifies modifiers of survival motor neuron protein. 2021

Nikki M McCormack, and Mahlet B Abera, and Eveline S Arnold, and Rebecca M Gibbs, and Scott E Martin, and Eugen Buehler, and Yu-Chi Chen, and Lu Chen, and Kenneth H Fischbeck, and Barrington G Burnett

Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, MD 20814, USA.

Spinal muscular atrophy (SMA) is a debilitating neurological disorder marked by degeneration of spinal motor neurons and muscle atrophy. SMA results from mutations in survival motor neuron 1 (SMN1), leading to deficiency of survival motor neuron (SMN) protein. Current therapies increase SMN protein and improve patient survival but have variable improvements in motor function, making it necessary to identify complementary strategies to further improve disease outcomes. Here, we perform a genome-wide RNAi screen using a luciferase-based activity reporter and identify genes involved in regulating SMN gene expression, RNA processing, and protein stability. We show that reduced expression of Transcription Export complex components increases SMN levels through the regulation of nuclear/cytoplasmic RNA transport. We also show that the E3 ligase, Neurl2, works cooperatively with Mib1 to ubiquitinate and promote SMN degradation. Together, our screen uncovers pathways through which SMN expression is regulated, potentially revealing additional strategies to treat SMA.

UI	MeSH Term	Description	Entries
D009046	Motor Neurons	Neurons which activate MUSCLE CELLS.	Neurons, Motor,Alpha Motorneurons,Motoneurons,Motor Neurons, Alpha,Neurons, Alpha Motor,Alpha Motor Neuron,Alpha Motor Neurons,Alpha Motorneuron,Motoneuron,Motor Neuron,Motor Neuron, Alpha,Motorneuron, Alpha,Motorneurons, Alpha,Neuron, Alpha Motor,Neuron, Motor
D005821	Genetic Techniques	Chromosomal, biochemical, intracellular, and other methods used in the study of genetics.	Genetic Technic,Genetic Technics,Genetic Technique,Technic, Genetic,Technics, Genetic,Technique, Genetic,Techniques, Genetic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D057166	High-Throughput Screening Assays	Rapid methods of measuring the effects of an agent in a biological or chemical assay. The assay usually involves some form of automation or a way to conduct multiple assays at the same time using sample arrays.	High-Throughput Screening,High-Throughput Biological Assays,High-Throughput Chemical Assays,High-Throughput Screening Methods,Assay, High-Throughput Biological,Assay, High-Throughput Chemical,Assay, High-Throughput Screening,Biological Assay, High-Throughput,Chemical Assay, High-Throughput,High Throughput Biological Assays,High Throughput Chemical Assays,High Throughput Screening,High Throughput Screening Assays,High Throughput Screening Methods,High-Throughput Biological Assay,High-Throughput Chemical Assay,High-Throughput Screening Assay,High-Throughput Screening Method,High-Throughput Screenings,Screening Assay, High-Throughput,Screening Method, High-Throughput,Screening, High-Throughput
D023281	Genomics	The systematic study of the complete DNA sequences (GENOME) of organisms. Included is construction of complete genetic, physical, and transcript maps, and the analysis of this structural genomic information on a global scale such as in GENOME WIDE ASSOCIATION STUDIES.	Functional Genomics,Structural Genomics,Comparative Genomics,Genomics, Comparative,Genomics, Functional,Genomics, Structural
D034622	RNA Interference	A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.	Gene Silencing, Post-Transcriptional,Post-Transcriptional Gene Silencing,Co-Suppression,Cosuppression,Posttranscriptional Gene Silencing,RNA Silencing,RNAi,Co Suppression,Gene Silencing, Post Transcriptional,Gene Silencing, Posttranscriptional,Gene Silencings, Posttranscriptional,Interference, RNA,Post Transcriptional Gene Silencing,Post-Transcriptional Gene Silencings,Silencing, Post-Transcriptional Gene