Biophysical Characterisation of Human LincRNA-p21 Sense and Antisense Alu Inverted Repeats

Biophysical Characterisation of Human LincRNA-p21 Sense and Antisense Alu Inverted Repeats

Abstract

Human 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.

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Authors
  • D’Souza, Michael H
  • Mrozowich, Tyler
  • Badmalia, Maulik D.
  • Geeraert, Mitchell
  • Frederickson, Angela
  • Henrickson, Amy
  • Demeler, Borries
  • Wolfinger, Michael T.
  • Patel, Trushar R.
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Shortfacts
Category
Journal Paper
Divisions
Bioinformatics and Computational Biology
Subjects
Computersimulation
Journal or Publication Title
Nucleic Acids Research
ISSN
0305-1048
Publisher
Oxford University Press
Page Range
pp. 5881-5898
Volume
50
Date
10 June 2022
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