Quantitative analysis of cryptic splicing associated with TDP-43 depletion.

ABSTRACT:

Background

Reliable exon recognition is key to the splicing of pre-mRNAs into mature mRNAs. TDP-43 is an RNA-binding protein whose nuclear loss and cytoplasmic aggregation are a hallmark pathology in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). TDP-43 depletion causes the aberrant inclusion of cryptic exons into a range of transcripts, but their extent, relevance to disease pathogenesis and whether they are caused by other RNA-binding proteins implicated in ALS/FTD are unknown.

Methods

We developed an analysis pipeline to discover and quantify cryptic exon inclusion and applied it to publicly available human and murine RNA-sequencing data.

Results

We detected widespread cryptic splicing in TDP-43 depletion datasets but almost none in another AL

SUBMITTER: Humphrey J 

PROVIDER: S-EPMC5446763 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature