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. 2015 Apr 15:6:142.
doi: 10.3389/fgene.2015.00142. eCollection 2015.

The interplay between DNA damage response and RNA processing: the unexpected role of splicing factors as gatekeepers of genome stability

Chiara Naro  1 , Pamela Bielli  1 , Vittoria Pagliarini  1 , Claudio Sette  1
Affiliations

The interplay between DNA damage response and RNA processing: the unexpected role of splicing factors as gatekeepers of genome stability

Chiara Naro et al. Front Genet. .

Abstract

Genome integrity is constantly threatened by endogenous and exogenous factors. However, its preservation is ensured by a network of pathways that prevent and/or repair the lesion, which constitute the DNA damage response (DDR). Expression of the key proteins involved in the DDR is controlled by numerous post-transcriptional mechanisms, among which pre-mRNA splicing stands out. Intriguingly, several splicing factors (SFs) have been recently shown to play direct functions in DNA damage prevention and repair, which go beyond their expected splicing activity. At the same time, evidence is emerging that DNA repair proteins (DRPs) can actively sustain the DDR by acting as post-transcriptional regulator of gene expression, in addition to their well-known role in the mechanisms of signaling and repair of the lesion. Herein, we will review these non-canonical functions of both SFs and DRPs, which suggest the existence of a tight interplay between splicing regulation and canonical DNA safeguard mechanisms ensuring genome stability.

Keywords: DNA damage prevention; DNA repair; DNA repair proteins; RNA binding proteins; RNA metabolism; genome stability; splicing factors.

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Figures

FIGURE 1
FIGURE 1
Non-canonical functions of splicing factors (SFs) and DNA repair proteins (DRPs) ensure genome stability. (A) SFs prevent transcription-related DNA insults such as R-loop formation. (B) SFs act as gatekeeper of cellular euploidy by regulating correct chromosomes segregation and preservation of telomeres integrity. (C) SFs actively participate to DNA repair processes. (D) DRPs regulate pre-mRNA splicing.
FIGURE 2
FIGURE 2
Examples of interplay between splicing factors (SFs) and DNA repair proteins (DRPs). (A) hnRNP C is recruited with the PALB2/BRCA2 complex at the DNA damage sites and it regulates proper splicing of its components. (B) Phosphorylated BRCA1 (pBRCA1) is recruited at the DNA lesions and it interacts with spliceosomal proteins favoring the correct splicing of DRPs encoding genes which sustain DNA damage response (DDR).
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