Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromatin samples were prepared from forty human brains. Chromatin was separated into a heavy heterochromatin fraction and two euchromatin fractions: intermediate euchromatin and light euchromatin. Employing a bacterial RNA polymerase as probe, only the euchromatin fractions were capable of RNA synthesis. In Control human brains, in brains of patients with dialysis dementia and in brains of elderly individuals without or with dementia of a type other than Alzheimer's disease, the euchromatin fractions accounted for about 75 per cent of the total DNA. In contrast, in brains of patients with advanced senile dementia or presenile dementia of the Alzheimer type, a wide range of euchromatin content was encountered with an average value of 55 per cent. Heterochromatization occurred in both neuron and glia enriched fractions suggesting that a major alteration in protein metabolism occurs in Alzheimer's disease.
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PMID:Altered chromatin conformation in Alzheimer's disease. 49 1

A large GGGGCC hexanucleotide repeat expansion in the first intron or promoter region of the C9orf72 gene is the most common genetic cause of familial and sporadic Amyotrophic lateral sclerosis (ALS), a devastating degenerative disease of motor neurons, and of Frontotemporal Dementia (FTD), the second most common form of presenile dementia after Alzheimer's disease. C9orf72-associated ALS/FTD is a multifaceted disease both in terms of its clinical presentation and the misregulated cellular pathways contributing to disease progression. Among the numerous pathways misregulated in C9orf72-associated ALS/FTD, altered RNA processing has consistently appeared at the forefront of C9orf72 research. This includes bidirectional transcription of the repeat sequence, accumulation of repeat RNA into nuclear foci sequestering specific RNA-binding proteins (RBPs) and translation of RNA repeats into dipeptide repeat proteins (DPRs) by repeat-associated non-AUG (RAN)-initiated translation. Over the past few years the true extent of RNA misprocessing in C9orf72-associated ALS/FTD has begun to emerge and disruptions have been identified in almost all aspects of the life of an RNA molecule, including release from RNA polymerase II, translation in the cytoplasm and degradation. Furthermore, several alterations have been identified in the processing of the C9orf72 RNA itself, in terms of its transcription, splicing and localization. This review article aims to consolidate our current knowledge on the consequence of the C9orf72 repeat expansion on RNA processing and draws attention to the mechanisms by which several aspects of C9orf72 molecular pathology converge to perturb every stage of RNA metabolism.
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PMID:RNA Misprocessing in C9orf72-Linked Neurodegeneration. 2874 2