Biology subjects

Tsao, L. H.

Publications and source records attributed to Tsao, L. H..

2 recordsLinked to original sources

bioRxiv2026

Interdependent RNA structural motifs at the 3'-terminus of the West Nile virus genome regulate viral growth

The RNA genome of West Nile Virus (WNV) folds into an elaborate series of RNA structural elements that are crucial for viral function. Among these elements, four pseudoknots (PKs) at the viral 3-terminus, designated as SLII, SLIV, DBI, and DBII, are among the most crucial players in the overall flaviviral lifecycle. While many studies have focused on exploring the behavior of individual PKs, we investigated the collective role of all four PKs in viral growth and small flaviviral RNA (sfRNA) formation. Through mutational analyses and infectious models, we establish that the four PKs are interdependent and work synergistically to aid in the folding and compaction of the WNV 3-terminal region. A striking hierarchy is observed in PK contributions to global folding and sfRNA formation, whereby SLIV plays the largest role, followed by DBI, DBII, and SLII. We also discover highly conserved RNA tertiary motifs within the PK assembly that are shared across flaviviruses, suggesting a new type of druggable target that may be of value in the search for pan-flaviviral therapeutics. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=63 SRC="FIGDIR/small/711107v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@14b10a5org.highwire.dtl.DTLVardef@131e63aorg.highwire.dtl.DTLVardef@1021aa9org.highwire.dtl.DTLVardef@12470a4_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

Structural basis for the function of long noncoding RNA Pnky in neural stem cells

LncRNA Pnky is a trans-acting regulator of neural stem cell (NSC) differentiation, but the molecular mechanisms by which Pnky regulates neurogenesis is unknown. A fundamental step towards mechanistic understanding is to determine whether a lncRNA has folded structure that underlies biological function. Using chemical probing and high-throughput analysis, we determined the secondary structure of Pnky folded in vitro and in cellulo. Pnky adopts a compact structure in vitro with distinct modules and evidence of tertiary interactions. In cellulo, Pnky structure is remarkably similar to the in vitro conformation. We used locked nucleic acid oligonucleotides to interrogate the entire Pnky transcript for function in NSCs and identified regions that when targeted increased neurogenesis - phenocopying Pnky knockdown - without decreasing transcript abundance. Our findings provide a structural basis for the role of Pnky in neurogenesis and, more broadly, illustrate how structural maps combined with phenotypic data can advance fundamental understanding of lncRNA mechanism. HIGHLIGHTSPnky folds into highly structured conformation in vitro with distinct modules. Pnky is a compact lncRNA with evidence of tertiary interactions. Pnky structure in neural stem cells is similar to its in vitro conformation. LNA ASO perturbations identify structured regions of Pnky involved in neuronal differentiation.

molecular biology↗