3′ UTR shortening represses tumor-suppressor genes in trans by disrupting ceRNA crosstalk

Hyun Jung Park, Ping Ji, Soyeon Kim, Zheng Xia, Benjamin Rodriguez, Lei Li, Jianzhong Su, Kaifu Chen, Chioniso P. Masamha, David Baillat, Camila R. Fontes-Garfias, Ann Bin Shyu, Joel R. Neilson, Eric J. Wagner, Wei Li

Research output: Contribution to journalArticle

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Abstract

Widespread mRNA 3′ UTR shortening through alternative polyadenylation1 promotes tumor growth in vivo2. A prevailing hypothesis is that it induces proto-oncogene expression in cis through escaping microRNA-mediated repression. Here we report a surprising enrichment of 3′UTR shortening among transcripts that are predicted to act as competing-endogenous RNAs (ceRNAs) for tumor-suppressor genes. Our model-based analysis of the trans effect of 3′ UTR shortening (MAT3UTR) reveals a significant role in altering ceRNA expression. MAT3UTR predicts many trans-targets of 3′ UTR shortening, including PTEN, a crucial tumor-suppressor gene3 involved in ceRNA crosstalk4 with nine 3′UTR-shortening genes, including EPS15 and NFIA. Knockdown of NUDT21, a master 3′ UTR-shortening regulator2, represses tumor-suppressor genes such as PHF6 and LARP1 in trans in a miRNA-dependent manner. Together, the results of our analysis suggest a major role of 3′ UTR shortening in repressing tumor-suppressor genes in trans by disrupting ceRNA crosstalk, rather than inducing proto-oncogenes in cis.

LanguageEnglish (US)
Pages1-7
Number of pages7
JournalNature Genetics
DOIs
StateAccepted/In press - May 21 2018
Externally publishedYes

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3' Untranslated Regions
Tumor Suppressor Genes
Proto-Oncogenes
MicroRNAs
Neoplasms
RNA
Messenger RNA
Growth
Genes

ASJC Scopus subject areas

  • Genetics

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3′ UTR shortening represses tumor-suppressor genes in trans by disrupting ceRNA crosstalk. / Park, Hyun Jung; Ji, Ping; Kim, Soyeon; Xia, Zheng; Rodriguez, Benjamin; Li, Lei; Su, Jianzhong; Chen, Kaifu; Masamha, Chioniso P.; Baillat, David; Fontes-Garfias, Camila R.; Shyu, Ann Bin; Neilson, Joel R.; Wagner, Eric J.; Li, Wei.

In: Nature Genetics, 21.05.2018, p. 1-7.

Research output: Contribution to journalArticle

Park, HJ, Ji, P, Kim, S, Xia, Z, Rodriguez, B, Li, L, Su, J, Chen, K, Masamha, CP, Baillat, D, Fontes-Garfias, CR, Shyu, AB, Neilson, JR, Wagner, EJ & Li, W 2018, '3′ UTR shortening represses tumor-suppressor genes in trans by disrupting ceRNA crosstalk' Nature Genetics, pp. 1-7. https://doi.org/10.1038/s41588-018-0118-8
Park, Hyun Jung ; Ji, Ping ; Kim, Soyeon ; Xia, Zheng ; Rodriguez, Benjamin ; Li, Lei ; Su, Jianzhong ; Chen, Kaifu ; Masamha, Chioniso P. ; Baillat, David ; Fontes-Garfias, Camila R. ; Shyu, Ann Bin ; Neilson, Joel R. ; Wagner, Eric J. ; Li, Wei. / 3′ UTR shortening represses tumor-suppressor genes in trans by disrupting ceRNA crosstalk. In: Nature Genetics. 2018 ; pp. 1-7.
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