The Role of Small Noncoding RNA in DNA Double-Strand Break Repair

Abstract

DNA damage is a common phenomenon promoted through a variety of exogenous and endogenous factors. The DNA damage response (DDR) pathway involves a wide range of proteins, and as was indicated, small noncoding RNAs (sncRNAs). These are double-strand break-induced RNAs (diRNAs) and DNA damage response small RNA (DDRNA). Moreover, RNA binding proteins (RBPs) and RNA modifications have also been identified to modulate diRNA and DDRNA function in the DDR process. Several theories have been formulated regarding the synthesis and function of these sncRNAs during DNA repair; nevertheless, these pathways’ molecular details remain unclear. Here, we review the current knowledge regarding the mechanisms of diRNA and DDRNA biosynthesis and discuss the role of sncRNAs in maintaining genome stability.

New Faces of old Friends: Emerging new Roles of RNA-Binding Proteins in the DNA Double-Strand Break Response

“…DilncRNAs are transcribed from and toward DNA ends whenever RNAP II binds to break-associated MRN (Figure 3B) (Michelini et al, 2017;Sharma et al, 2021). They have important roles in the recruitment of DSB signaling factors and also serve as precursors for the Drosha and Dicer-dependent generation of DNA damage response small RNAs (DDRNAs) (Francia et al, 2012;Michelini et al, 2017;Rossiello et al, 2017;Gioia et al, 2019;Rzeszutek and Betlej, 2020).…”

“…At DSBs, RNAP II also promotes the generation of DSBinduced RNAs (diRNAs), which are produced when local RNA transcripts become double-stranded and are then processed by Dicer into double-stranded small RNAs (Wei et al, 2012;Yang and Qi, 2015;Rzeszutek and Betlej, 2020). In Arabidopsis thaliana, the generation of double-stranded RNAs depends on RNA-dependent RNA polymerases that use RNA transcripts as templates (Wei et al, 2012;Miki et al, 2017;Rzeszutek and Betlej, 2020). However, how single-stranded RNA transcripts become double-stranded RNAs in human cells remains unclear.…”

Molecular Mechanisms of Specific Cellular DNA Damage Response and Repair Induced by the Mixed Radiation Field During Boron Neutron Capture Therapy

“…RNA transcripts and DDR proteins are known to interact functionally (40). Many recent studies have reported the pivotal role of ncRNAs in DNA repair and genomic rearrangements in different research models (41)(42)(43)(44). There is growing evidence that ncRNAs regulate the DDR, especially small microRNAs (miRNAs), which are induced at DNA-DSBs, thus mediating repair (23,41,45).…”

“…Many recent studies have reported the pivotal role of ncRNAs in DNA repair and genomic rearrangements in different research models (41)(42)(43)(44). There is growing evidence that ncRNAs regulate the DDR, especially small microRNAs (miRNAs), which are induced at DNA-DSBs, thus mediating repair (23,41,45). Regulatory short miRNAs are ncRNAs encoded in intronic regions of proteincoding genes or in the intergenic regions of the genome (23,42).…”

“…Regulatory short miRNAs are ncRNAs encoded in intronic regions of proteincoding genes or in the intergenic regions of the genome (23,42). Small ncRNAs generated at DNA-DSBs, critical for DDR activation, are termed DDR small RNAs (DDRNAs) and are described in details in a review by Rzeszutek et al (41). It is considered that some small ncRNAs can regulate the expression of genes encoding DDR proteins, especially those involved in DSB repair; however, the mechanisms are not fully understood (45).…”