SEARCH · PubMed Health

Results for “SHAPE-MaP”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

2 recordsLinked to original sources

PubMed2026

CONCR lncRNA organizes a 3'-end structural domain that engages DDX11 for DNA replication and sister chromatid cohesion.

CONCR (DDX11-AS1) is a long noncoding RNA (lncRNA) necessary for the establishment of sister chromatid cohesion. Despite its activity, whether it contains structural elements essential for its function remains unknown. We determined CONCR structural organization and its functional relevance by integrating selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP), atomic force microscopy (AFM), evolutionary analyses, cryo-electron microscopy (cryo-EM), and cellular genetic studies. We found that CONCR molecular topology is modular, with highly structured domains connected by flexible linkers. A large 3'-end domain is responsible for binding to DDX11 helicase, can trigger DDX11 ATPase activity, and is essential for proper DNA replication and sister chromatid cohesion. This 3' end comprises two helical arms connecting two multiway junctions with structural motifs conserved among all primate groups and required for DDX11 binding and sister chromatid cohesion. Our results highlight the critical role of RNA structure in CONCR function, with a highly structured 3'-end domain acting as a loading and activation platform for DDX11 helicase.

DEAD-box RNA Helicases↗

PubMed2025

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.

LNA-ASOs↗