Post by Tharun Selvam Mahendran

In our recent work published in Nature Chemistry, we report that biomolecular condensates (or membraneless organelles) can enhance the aggregation of repeat RNAs, including GC-rich sequences associated with several neurodegenerative disorders. Using a combination of quantitative microscopy techniques—including video particle tracking-based nanorheology, temperature-controlled microscopy, and optical tweezer-based measurements—we demonstrate that RNA aggregation within the condensate microenvironment is accompanied by a liquid-to-solid phase transition. We found that multivalent RNA-binding proteins, such as G3BP1, can act as RNA chaperones, suppressing RNA aggregation. We further demonstrate that antisense oligonucleotides (ASOs) can be rationally designed to reverse RNA aggregation within biomolecular condensates. I extend my sincerest appreciation to my advisor, PRIYA R. BANERJEE, for his unwavering guidance and support; to my brilliant co-authors for their invaluable contributions; and to our collaborators, lab members, and peers whose insights helped shape this study. Link to our Nature Portfolio article: https://lnkd.in/g3TQRE6u