Long non-coding RNA LIP interacts with PARP-1 influencing the efficiency of base excision repair

Abstract

In recent years, various long non-coding RNAs (lncRNAs) involved in DNA damage response (DDR) have been identified and studied to deepen our understanding. However, there are rare reports on the association between lncRNAs and base excision repair (BER). Our designed DNA microarray identified dozens of functionally unknown lncRNAs, and their transcription levels significantly increased upon exposure to DNA damage inducers. One of them, named LIP (Long noncoding RNA Interacts with PARP-1), exhibited a significant alteration in transcription in response to methyl methanesulfonate (MMS) and temozolomide (TMZ) treatments. LIP knockdown or knockout cell lines are sensitive to MMS and TMZ, indicating that LIP plays a crucial role in DDR. The loss or insufficiency of LIP significantly influences the efficiency of BER in human cells, and it suggests that LIP participates in the BER pathway. The interaction between LIP and a key factor in BER, poly (ADP-ribose) polymerase 1 (PARP-1), has been confirmed. We identified and characterized LIP, a lncRNA, which is involved in DDR, significantly influences BER efficiency, and interacts with the BER key factor PARP-1. This advances our understanding of the connection between lncRNAs and BER, presenting the potential for the discovery of new drug targets.

Keywords

• Long non-coding RNAs
• LIP
• DNA damage response
• Base excision repair
• Poly (ADP-ribose) polymerase 1