hnRNPB1-mediated HOTAIR restructuring for RNA−RNA interactions
Long non-coding RNAs (lncRNAs) regulate chromatin activity by interacting with chromatin modifiers, where they act as scaffolds. One such lncRNA is HOTAIR, which is transcribed from HOX_C motifs and involved in gene regulation by silencing various tumor and metastasis suppressing genes. In cancerous conditions, the levels of HOTAIR are upregulated, triggering PRC2-mediated silencing through altered methylation activity, which promotes tumor invasiveness and metastasis. LncRNA HOTAIR also recruits the hnRNPB1 protein. Upon binding of the hnRNPB1 protein, structural rearrangement takes place, disrupting the site of PRC2 binding and facilitating RNA-RNA interactions between HOTAIR and neighbouring transcript. The RNA-RNA interaction removes the inhibitory effect of the PRC2 complex, further enhancing its methylation activity. Dr Niyati Jain’s lab shed light on the mechanism by which the hnRNPB1 protein recognizes lncRNA HOTAIR and leads to structural rearrangement. They looked at the helix-12 region of HOTAIR, which is sufficient to bind with the hnRNPB1 protein, and this binding is structure-mediated rather than sequence-dependent. They showed that the low complexity domain (LCD) of the hnRNPB1 protein binds cooperatively with the tandem RRMs towards the lncRNA. Their study suggests that the LCD of hnRNPB1 protein acts as an RNA chaperon, triggering the structural modification of HOTAIR. The unwinding of the helix-12 region by the LCD makes it possible to form an RNA:RNA hotspot, thus regulating the activities of nascent transcripts.
Interaction of hnRNPB1 with Helix-12 of hHOTAIR Reveals the Distinctive Mode of RNA Recognition That Enables the Structural Rearrangement by LCD. Kumar A, Daripa P, Maiti S, Jain N. Biochemistry. 2023 Jun 12. doi: 10.1021/acs.biochem.3c00181. Online ahead of print.
Multisampling-based docking reveals Imidazolidinyl urea as a multitargeted inhibitor for lung cancer: an optimisation followed multi-simulation and in-vitro study. Ahmad S, Singh V, Gautam HK, Raza K. J Biomol Struct Dyn. 2023 May 8:1-18. doi: 10.1080/07391102.2023.2209673. Online ahead of print.