Transcriptional mutagenesis reduces splicing fidelity in mammalian cells.

ABSTRACT: Splicing fidelity is essential to the maintenance of cellular functions and viability, and mutations or natural variations in pre-mRNA sequences and consequent alteration of splicing have been implicated in the etiology and progression of numerous diseases. The extent to which transcriptional errors or lesion-induced transcriptional mutagenesis (TM) influences splicing fidelity is not currently known. To investigate this, we employed site-specific DNA lesions on the transcribed strand of a minigene splicing reporter in normal mammalian cells. These were the common mutagenic lesions O6-methylguanine (O6-meG) and 8-oxoguanine (8-oxoG). The minigene splicing reporters were derived from lamin A (LMNA) and proteolipid protein 1 (PLP1), both with known links to human diseases that result from de

SUBMITTER: Paredes JA 

PROVIDER: S-EPMC5499639 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature