RNA and Senescence

PI: Marta Montes

Long non-coding RNAs (lncRNAs) are long RNA molecules that do not code for proteins and are involved in cellular functions, both in physiological conditions and in pathologies. Due to their specific expression pattern, in our laboratory we are interested in studying these molecules as potential markers to detect senescent cells and as targets for their elimination. 

Our objectives are: 

• Identify lncRNAs that are specifically expressed in senescent cells 
• Determine the functional role of lncRNAs in therapy-induced senescence 
• Investigate the therapeutic potential of lncRNAs"

PI: Marta Montes

The deposition of chemical modifications on the RNA introduces functional diversity in the transcriptome beyond the DNA sequence. These post-transcriptional modifications on the RNA, termed “epitranscriptomics”, have emerged as novel regulators of gene expression. RNA modifications can influence RNA structure or RNA interactions with other molecules modulating RNA metabolism and function becoming an additional layer of regulation. We hypothesize that specific RNA modifications are important for the senescence response to chemotherapy treatment. Targeting the regulatory modification pathways in therapy-induced senescence will allow to improve cancer treatment. 

The objectives of this line of research are:

• Identify specific RNA modifications and RNA modifiers that are deregulated in therapy-induced senescence in ovarian cancer. 
• Characterize the molecular mechanism of the senescence-specific RNA modification in vitro. 
• Investigation the therapeutic potential of targeting the senescence-specific RNA modification in vivo. 

PI: Marta Montes

Recent research suggests a complex interaction between metabolic enzymes and RNA. Preliminary data from our laboratory has shown that DLST, an enzyme of the tricarboxylic acid (TCA) cycle, interacts with a specific lncRNA during oncogene-induced senescence. This interaction allows for the proper localization and function of DLST within the cell. Based on these previous studies in our laboratory, our hypothesis is that RNA, through its interaction with metabolic enzymes, contributes to cellular metabolic reprogramming in response to the induction of TIS in ovarian cancer. 

In collaboration with national and international groups, our general objective is to identify the metabolic enzymes that interact with RNA in therapy-induced senescence and the metabolic consequences of such interaction.