• Media type: E-Article
  • Title: Biophysical characterisation of human LincRNA-p21 sense and antisense Alu inverted repeats
  • Contributor: D’Souza, Michael H; Mrozowich, Tyler; Badmalia, Maulik D; Geeraert, Mitchell; Frederickson, Angela; Henrickson, Amy; Demeler, Borries; Wolfinger, Michael T; Patel, Trushar R
  • Published: Oxford University Press (OUP), 2022
  • Published in: Nucleic Acids Research, 50 (2022) 10, Seite 5881-5898
  • Language: English
  • DOI: 10.1093/nar/gkac414
  • ISSN: 0305-1048; 1362-4962
  • Origination:
  • Footnote:
  • Description: AbstractHuman Long Intergenic Noncoding RNA-p21 (LincRNA-p21) is a regulatory noncoding RNA that plays an important role in promoting apoptosis. LincRNA-p21 is also critical in down-regulating many p53 target genes through its interaction with a p53 repressive complex. The interaction between LincRNA-p21 and the repressive complex is likely dependent on the RNA tertiary structure. Previous studies have determined the two-dimensional secondary structures of the sense and antisense human LincRNA-p21 AluSx1 IRs using SHAPE. However, there were no insights into its three-dimensional structure. Therefore, we in vitro transcribed the sense and antisense regions of LincRNA-p21 AluSx1 Inverted Repeats (IRs) and performed analytical ultracentrifugation, size exclusion chromatography, light scattering, and small angle X-ray scattering (SAXS) studies. Based on these studies, we determined low-resolution, three-dimensional structures of sense and antisense LincRNA-p21. By adapting previously known two-dimensional information, we calculated their sense and antisense high-resolution models and determined that they agree with the low-resolution structures determined using SAXS. Thus, our integrated approach provides insights into the structure of LincRNA-p21 Alu IRs. Our study also offers a viable pipeline for combining the secondary structure information with biophysical and computational studies to obtain high-resolution atomistic models for long noncoding RNAs.
  • Access State: Open Access