Length and secondary structure of the 5' non-coding regions of mouse p53 mRNA transcripts - mouse as a model organism for p53 gene expression studies

RNA Biol. 2019 Jan;16(1):25-41. doi: 10.1080/15476286.2018.1556084. Epub 2018 Dec 20.

Abstract

Transcription initiation sites of Trp53 gene in mice were determined using the 5'RACE method. Based on sequence alignment of the 5'-terminal regions of p53 mRNA in mammals, the site for the most abundant transcript turned out to be essentially identical with that determined for human TP53 gene and slightly differed for the longest transcripts, in mice and humans. Secondary structures of the 5' -terminal regions of the shorter, most abundant and the longest mouse transcripts were determined in vitro and the shorter transcript was also mapped in transfected mouse cells. For the first time, secondary structure models of the 5' terminus of two mouse p53 mRNAs were proposed. Comparing these models with the conservativeness of the nucleotide sequence of the 5'-terminal region of mRNA in mouse and other mammals, the possible function of the selected structural domains of this region was discussed. To elucidate the translation mechanisms, the two studied mRNAs were translated in the presence of an increasing concentration of the cap analog. For the longest transcript, the data suggested that IRES element(s) was/were involved in translation initiation. Additionally, changes in p53 synthesis under genotoxic and endoplasmic reticulum stress conditions in mouse cells were analyzed.

Keywords: 5ʹRACE; 5ʹUTR; 5′ non-coding region; Mouse p53 mRNA; RNA secondary structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions*
  • Animals
  • Base Sequence
  • Cell Line
  • Conserved Sequence
  • Gene Expression Regulation*
  • Internal Ribosome Entry Sites
  • Mice
  • Nucleic Acid Conformation*
  • Peptide Chain Initiation, Translational
  • RNA Folding
  • RNA, Messenger / chemistry*
  • RNA, Messenger / genetics*
  • Response Elements
  • Transcription Initiation Site
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • 5' Untranslated Regions
  • Internal Ribosome Entry Sites
  • RNA, Messenger
  • Tumor Suppressor Protein p53

Grants and funding

This work was supported by the Polish National Centre of Science 2013/09/B/NZ1/01884 and 2016/21/B/NZ1/02832. This publication was also supported by the Polish Ministry of Science and Higher Education, under the KNOW program, and under Grant from the Institute of Bioorganic Chemistry PAS for young researches and PhD students.