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Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43
It is found that TDP-43 autoregulates its synthesis, in part by directly binding and enhancing splicing of an intron in the 3′ untranslated region of its own transcript, thereby triggering nonsense-mediated RNA degradation. Expand
miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting.
IMR-122 inhibition in a diet-induced obesity mouse model resulted in decreased plasma cholesterol levels and a significant improvement in liver steatosis, accompanied by reductions in several lipogenic genes, suggesting that miR- 122 may be an attractive therapeutic target for metabolic disease. Expand
The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation.
Evidence is provided for a role for the long nuclear-retained regulatory RNA, MALAT1 in AS regulation and for the role for an nrRNA in the regulation of gene expression, which suggests that MALat1 regulates AS by modulating the levels of active SR proteins. Expand
Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs
Depletion of FUS/TLS from the adult nervous system altered the levels or splicing of >950 mRNAs, most of which are distinct from RNAs dependent on TDP-43, supporting a common loss-of-function pathway as one component underlying motor neuron death from misregulation of T DP-43 or FUS-43. Expand
RNA Toxicity from the ALS/FTD C9ORF72 Expansion Is Mitigated by Antisense Intervention
Data indicate a toxic RNA gain-of-function mechanism as a cause of C9ORF72 ALS and provide candidate antisense therapeutics and candidate human pharmacodynamic markers for therapy. Expand
Targeting RNA Foci in iPSC-Derived Motor Neurons from ALS Patients with a C9ORF72 Repeat Expansion
Findings support the idea that the buildup of “toxic” RNA containing the GGGGCC repeat contributes to the death of motor neurons in ALS, and suggest that antisense oligonucleotides targeting this transcript may be a strategy for treating ALS patients with the C9ORF72 repeat expansion. Expand
RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform.
  • C. Bennett, E. Swayze
  • Biology, Medicine
  • Annual review of pharmacology and toxicology
  • 6 January 2010
The molecular mechanisms by which antisense oligonucleotides can be designed to modulate RNA function in mammalian cells and how synthetic oligon nucleotides behave in the body are focused on. Expand
Regulating Gene Expression through RNA Nuclear Retention
A role of the cell nucleus in harboring RNA molecules that are not immediately needed to produce proteins but whose cytoplasmic presence is rapidly required upon physiologic stress is revealed. Expand
MicroRNA-143 Regulates Adipocyte Differentiation*
It is reported that the combination of expression data and functional assay results identified a role for miR-143 in adipocyte differentiation and may act through target gene ERK5. Expand
Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration
Sustained ASO-mediated lowering of C9orf72 RNAs throughout the CNS of mice is demonstrated to be well tolerated, producing no behavioral or pathological features characteristic of ALS/FTD and only limited RNA expression alterations. Expand