Spliceosomal components protect embryonic neurons from R-loop-mediated DNA damage and apoptosis.

ABSTRACT: RNA splicing factors are essential for the viability of all eukaryotic cells; however, in metazoans some cell types are exquisitely sensitive to disruption of splicing factors. Neuronal cells represent one such cell type, and defects in RNA splicing factors can lead to neurodegenerative diseases. The basis for this tissue selectivity is not well understood owing to difficulties in analyzing the consequences of splicing factor defects in whole-animal systems. Here, we use zebrafish mutants to show that loss of spliceosomal components, including splicing factor 3b, subunit 1 (sf3b1), causes increased DNA double-strand breaks and apoptosis in embryonic neurons. Moreover, these mutants show a concomitant accumulation of R-loops, which are non-canonical nucleic acid structures tha

SUBMITTER: Sorrells S 

PROVIDER: S-EPMC5894942 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature