Identification and Characterization of Functional LncRNA Regulation of Mitochondrial Respiration
Carolina Khoury, Dr. Assaf C. Bester
The central dogma of molecular biology traditionally emphasizes RNA’s role as a messenger, bridging the information repository in DNA with protein synthesis at the ribosome. However, the human genome encodes a vast array of non-protein-coding RNA (ncRNA) molecules with diverse functions. In fact, in many species, protein-coding genes comprise only a small fraction of the total genome.
Among ncRNAs, long non-coding RNAs (lncRNAs)–transcripts longer than 200 nucleotides that are not translated into proteins–represent the largest and most heterogeneous group of RNA in the human genome Recent research has begun to uncover lncRNAs’ diverse roles, linking them to various biological processes and diseases, including apoptosis, metastasis, proliferation, and metabolism.
Metabolic rewiring is pivotal in cancer, emphasizing the need to identify genes that regulate both normal and malignant metabolism. While protein-coding genes’ functions are well-studied, the complex interactions between lncRNAs and cellular metabolism remain largely uncharted .
This study employed screening techniques to identify lncRNAs influencing mitochondrial respiration in leukemia cells, pinpointing four lncRNAs that significantly affect energy metabolism and cellular fitness. Through cell-based assays and molecular characterization, a regulatory network impacting mitochondrial function was revealed. Notably, the research highlights the lncRNA known as the negative regulator of P-body association (NBDY) in controlling multiple metabolic genes.
Further investigation of NBDY’s mechanisms and potential therapeutic applications will enrich our understanding of metabolic regulation. The findings not only contribute to our understanding of RNA biology but also may open new avenues for therapeutic interventions in metabolic diseases.