Signaling landscape of mitochondrial non-coding RNAs

Abstract

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

Keywords:

• Nucleic acids
• interactions networks
• pathways
• signaling
• gene regulation

Acknowledgements

We acknowledge Center for International Mobility (CIMO) Finland, for the grant support. We thank CSC (Finnish IT Center for Science) for providing us with a computational facility to carry out the research work. We also thank Ms. Nilakhi Poddar for the computational research assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

M.G. performed the data analysis. O.Y and M.K conceived the approach. M.G. implemented the methods and performed analysis. A.M, T.R and K.S checked the sources and data, M.G, A.M, T.R and K.S revised wrote the paper. M.K managed all studies. All the authors contributed to writing the manuscript.

Data availability statement

The data used in this study are available in the following public repositories. (The complete Human mitochondrial DNA sequence - https://www.ncbi.nlm.nih.gov/nuccore/251831106; Non-coding mitochondrial sequence entries - Supplementary material of Ro et al. (2013), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674384/; Uniprot - https://www.uniprot.org/help/uniprotkb; Protein Data Bank - https://www.rcsb.org/).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.