Signaling landscape of mitochondrial non-coding RNAs

Human mitochondria are the vital cell organelle acting as a storehouse of energy generation and diverse regulatory functions. Mitochondrial DNA comprises 93% coding region and 7% non-coding regions, in which the non-coding region hypothesized as responsible for signaling is our specific interest. Here, we explored the unknown functions of mitochondrial non-coding RNAs by studying their respective signaling pathways. We retrieved conserved motifs of interactions from known experimental protein-RNA complexes to model unknown mitochondrial ncRNA sequences. Our results provide the ncRNAs list and show their involvement in four crucial pathways, such as (i) Processing of Capped Intron-Containing Pre-mRNA, (ii) Spliceosome, (iii) Spliceosomal assembly, and (iv) RNA Polymerase II Transcription, respectively. The interactome analysis revealed that the SRSF2 and U2AF2 proteins interact with ncRNAs. Further, we have simulated the selected ncRNA-protein complexes in cell-like environmental conditions and found them stable in terms of energetics. Through our study, we have identified an apparent interaction of mitochondrial ncRNAs with proteins and their role in critical signaling pathways, providing new insights into mitochondrial ncRNA-dependent gene regulation. Communicated by Ramaswamy H. Sarma.