New Roles for Canonical Transcription Factors in Repeat Expansion Diseases.

New Roles for Canonical Transcription Factors in Repeat Expansion Diseases. Trends Genet. 2019 Dec 11;: Authors: Goodman LD, Bonini NM Abstract The presence of microsatellite repeat expansions within genes is associated with >30 neurological diseases. Of interest, (GGGGCC)>30-repeats within C9orf72 are associated with amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). These expansions can be 100s to 1000s of units long. Thus, it is perplexing how RNA-polymerase II (RNAPII) can successfully transcribe them. Recent investigations focusing on GGGGCC-transcription have identified specific, canonical complexes that may promote RNAPII-transcription at these GC-rich microsatellites: the DSIF complex and PAF1C. These complexes may be important for resolving the unique secondary structures formed by GGGGCC-DNA during transcription. Importantly, this process can produce potentially toxic repeat-containing RNA that can encode potentially toxic peptides, impacting neuron function and health. Understanding how transcription of these repeats occurs has implications for therapeutics in multiple diseases. PMID: 31837826 [PubMed - as supplied by publisher]
Source: Trends in Genetics : TIG - Category: Genetics & Stem Cells Authors: Tags: Trends Genet Source Type: research