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The findings that amyotrophic lateral sclerosis (ALS) patients almost universally display pathological mislocalization of the RNA-binding protein TDP-43 and that mutations in its gene cause familial ALS have nominated altered RNA metabolism as a disease mechanism. However, the RNAs regulated by TDP-43 in motor neurons and their connection to neuropathy remain to be identified. Here we report transcripts whose abundances in human motor neurons are sensitive to TDP-43 depletion. Notably, expression of STMN2, which encodes a microtubule regulator, declined after TDP-43 knockdown and TDP-43 mislocalization as well as in patient-specific motor neurons and postmortem patient spinal cord. STMN2 loss upon reduced TDP-43 function was due to altered splicing, which is functionally important, as we show STMN2 is necessary for normal axonal outgrowth and regeneration. Notably, post-translational stabilization of STMN2 rescued neurite outgrowth and axon regeneration deficits induced by TDP-43 depletion. We propose that restoring STMN2 expression warrants examination as a therapeutic strategy for ALS.
Pubmed ID: 30643292
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Commercial organization for research and development genomics services and technical support to researchers.
View all literature mentionsSoftware package providing an approximation method to determine relative gene expression with quantitative real-time PCR (qRT-PCR) experiments. It requires no standard curve for each primer-target pair, therefore reducing the working load and yet returning accurate enough results as long as the assumptions of the amplification efficiency hold. The package implements a pipeline to collect, analyze and visualize qRT-PCR results, for example those from TaqMan SDM software, mainly using the ddCt method. The pipeline can be either invoked by a script in command-line or through the API consisting of S4-Classes, methods and functions.
View all literature mentionsCommercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsA research center associated with the University of Pittsburgh that specializes in the diagnosis of Alzheimer's disease and related disorders. The overall objective of the ADRC is to study the pathophysiology of Alzheimer's disease, with the aim of improving the reliability of diagnosis of Alzheimer's and developing effective treatment strategies. Current research foci emphasize neuropsychiatry and neuropsychology, molecular genetics and epidemiology, basic neuroscience, and structural and functional imaging that aid in the diagnosis and treatment of Alzheimer's disease. Specific services at the ADRC include: comprehensive diagnostic evaluation of patients with suspected Alzheimer's disease and other forms of dementia; evaluation of memory, language, judgment, and other cognitive abilities; and education and counseling for patients and families.
View all literature mentionsAn antibody supplier which banks and distributes hybridomas and monoclonal antibodies for use in research. The bank includes antibodies against targets such as GFP, transcription factors, stem cells, and human.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
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