Eukaryotic cells tightly regulate gene expression through diverse post-transcriptional mechanisms, which are essential for cell survival, proliferation, and differentiation. Dysregulation of gene expression is often linked to cellular stress and various diseases, including cancers and viral infections. However, current understanding of the regulatory processes driving these alterations in gene expression, as well as their physiological functions, remains limited. Our research aims to study the molecular details of RNA-mediated gene regulation in these pathological contexts. Specifically, we investigate riboregulators, RNA-binding protein (RBP)-RNA interplays, cis-acting RNA elements and their roles in modulating cell signalling pathways and translational control.

To address this, we employ an integrative approach combining computational analyses, biochemical and molecular techniques, and advanced in-cell RNA structure probing methods. The insights gained from our studies aim to uncover how post-transcriptional gene regulation can be targeted for therapeutic interventions in cancer and viral infections.

Selected Publications:

1. Fusée L^#, Salomao N, Ponnuswamy A, Wang L, López I, Chen S, Gu X, Polyzoidis S, Gnanasundram SV^#*, Fahraeus R*. The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures. Cell Death Differ. 2023 Apr;30(4):1072-1081.

2. Gu X, Wang L, Coates PJ, Gnanasundram SV, Sgaramella N, Sörlin J, Erdogan B, Magan M, Nylander K. Evidence for etiologic field changes in tongue distant from tumor in patients with squamous cell carcinoma of the oral tongue. J Pathol. 2023 Jan;259(1):93-102.

3. Bonczek O, Wang L, Gnanasundram SV, Chen S, Haronikova L, Zavadil-Kokas F, Vojtesek B. DNA and RNA Binding Proteins: From Motifs to Roles in Cancer. Int J Mol Sci. 2022 Aug 18;23(16):9329.

4. Gnanasundram SV*, Bonczek O, Wang L, Chen S, Fahraeus R. p53 mRNA Metabolism Links with the DNA Damage Response. Genes (Basel). 2021 Sep 20;12(9):1446.

5. Gnanasundram SV, Malbert-Colas L, Chen S, Fusée L, Daskalogianni C, Muller P, Salomao N, Fåhraeus R. MDM2's dual mRNA binding domains co-ordinate its oncogenic and tumour suppressor activities. Nucleic Acids Res. 2020 Jul 9;48(12):6775-6787.

6. Gnanasundram SV, Kos-Braun IC, Koš M. At least two molecules of the RNA helicase Has1 are simultaneously present in pre-ribosomes during ribosome biogenesis. Nucleic Acids Res. 2019 Nov 18;47(20):10852-10864.

7. Gnanasundram SV*, Fåhraeus R*. Translation Stress Regulates Ribosome Synthesis and Cell Proliferation. Int J Mol Sci. 2018 Nov 27;19(12):3757.

8. Karakostis K, Gnanasundram SV, López I, Thermou A, Wang L, Nylander K, Olivares-Illana V, Fåhraeus R. A single synonymous mutation determines the phosphorylation and stability of the nascent protein. J Mol Cell Biol. 2019 Mar 1;11(3):187-199.

9. Gnanasundram SV, Pyndiah S, Daskalogianni C, Armfield K, Nylander K, Wilson JB, Fåhraeus R. PI3Kδ activates E2F1 synthesis in response to mRNA translation stress. Nat Commun. 2017 Dec 13;8(1):2103.

10. Gnanasundram SV, Koš M. Fast protein-depletion system utilizing tetracycline repressible promoter and N-end rule in yeast. Mol Biol Cell. 2015 Feb 15;26(4):762-8.

11. Bhat P^#, Gnanasundram SV^#, Mani P, Ray PS, Sarkar DP, Das S. Targeting ribosome assembly on the HCV RNA using a small RNA molecule. RNA Biol. 2012 Aug;9(8):1110-9.

12. Verma B, Ponnuswamy A, Gnanasundram SV, Das S. Cryptic AUG is important for 48S ribosomal assembly during internal initiation of translation of coxsackievirus B3 RNA. J Gen Virol. 2011 Oct;92(Pt 10):2310-2319.

13. Subramanian N, Mani P, Roy S, Gnanasundram SV, Sarkar DP, Das S. Targeted delivery of hepatitis C virus-specific short hairpin RNA in mouse liver using Sendai virosomes. J Gen Virol. 2009 Aug;90(Pt 8):1812-1819.

*-corresponding author

#-joined first author