Translation of human Δ133p53 mRNA and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mRNA.

The p53 protein is expressed as at least twelve protein isoforms. Within intron 4 of the human TP53 gene, a P2 transcription initiation site is located and this transcript encodes two p53 isoforms: Δ133p53 and Δ160p53. Here, the secondary structure of the 5'-terminal region of P2-initiated mRNA...

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Autores principales:	Paulina Żydowicz-Machtel, Mariola Dutkiewicz, Agata Swiatkowska, Dorota Gurda-Woźna, Jerzy Ciesiołka
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/58104ef2ee3e40c29e2fdfe9a66fa15d
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spelling	oai:doaj.org-article:58104ef2ee3e40c29e2fdfe9a66fa15d2021-12-02T20:08:29ZTranslation of human Δ133p53 mRNA and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mRNA.1932-620310.1371/journal.pone.0256938https://doaj.org/article/58104ef2ee3e40c29e2fdfe9a66fa15d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256938https://doaj.org/toc/1932-6203The p53 protein is expressed as at least twelve protein isoforms. Within intron 4 of the human TP53 gene, a P2 transcription initiation site is located and this transcript encodes two p53 isoforms: Δ133p53 and Δ160p53. Here, the secondary structure of the 5'-terminal region of P2-initiated mRNA was characterized by means of the SHAPE and Pb2+-induced cleavage methods and for the first time, a secondary structure model of this region was proposed. Surprisingly, only Δ133p53 isoform was synthetized in vitro from the P2-initiated p53 mRNA while translation from both initiation codons occurred after the transfection of vector-encoded model mRNA to HCT116 cells. Interestingly, translation performed in the presence of the cap analogue suggested that the cap-independent process contributes to the translation of P2-initiated p53 mRNA. Subsequently, several antisense oligonucleotides targeting the 5'-terminal region of P2-initiated p53 mRNA were designed. The selected oligomers were applied in in vitro translation assays as well as in cell lines and their impact on the Δ133p53 synthesis and on cell viability was investigated. The results show that these oligomers are attractive tools in the modulation of the translation of P2-initiated p53 mRNA through attacking the 5' terminus of the transcript. Since cell proliferation is also reduced by antisense oligomers that lower the level of Δ133p53, this demonstrates an involvement of this isoform in tumorigenesis.Paulina Żydowicz-MachtelMariola DutkiewiczAgata SwiatkowskaDorota Gurda-WoźnaJerzy CiesiołkaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0256938 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paulina Żydowicz-Machtel Mariola Dutkiewicz Agata Swiatkowska Dorota Gurda-Woźna Jerzy Ciesiołka Translation of human Δ133p53 mRNA and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mRNA.
description	The p53 protein is expressed as at least twelve protein isoforms. Within intron 4 of the human TP53 gene, a P2 transcription initiation site is located and this transcript encodes two p53 isoforms: Δ133p53 and Δ160p53. Here, the secondary structure of the 5'-terminal region of P2-initiated mRNA was characterized by means of the SHAPE and Pb2+-induced cleavage methods and for the first time, a secondary structure model of this region was proposed. Surprisingly, only Δ133p53 isoform was synthetized in vitro from the P2-initiated p53 mRNA while translation from both initiation codons occurred after the transfection of vector-encoded model mRNA to HCT116 cells. Interestingly, translation performed in the presence of the cap analogue suggested that the cap-independent process contributes to the translation of P2-initiated p53 mRNA. Subsequently, several antisense oligonucleotides targeting the 5'-terminal region of P2-initiated p53 mRNA were designed. The selected oligomers were applied in in vitro translation assays as well as in cell lines and their impact on the Δ133p53 synthesis and on cell viability was investigated. The results show that these oligomers are attractive tools in the modulation of the translation of P2-initiated p53 mRNA through attacking the 5' terminus of the transcript. Since cell proliferation is also reduced by antisense oligomers that lower the level of Δ133p53, this demonstrates an involvement of this isoform in tumorigenesis.
format	article
author	Paulina Żydowicz-Machtel Mariola Dutkiewicz Agata Swiatkowska Dorota Gurda-Woźna Jerzy Ciesiołka
author_facet	Paulina Żydowicz-Machtel Mariola Dutkiewicz Agata Swiatkowska Dorota Gurda-Woźna Jerzy Ciesiołka
author_sort	Paulina Żydowicz-Machtel
title	Translation of human Δ133p53 mRNA and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mRNA.
title_short	Translation of human Δ133p53 mRNA and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mRNA.
title_full	Translation of human Δ133p53 mRNA and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mRNA.
title_fullStr	Translation of human Δ133p53 mRNA and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mRNA.
title_full_unstemmed	Translation of human Δ133p53 mRNA and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mRNA.
title_sort	translation of human δ133p53 mrna and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mrna.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/58104ef2ee3e40c29e2fdfe9a66fa15d
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Translation of human Δ133p53 mRNA and its targeting by antisense oligonucleotides complementary to the 5'-terminal region of this mRNA.

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