MRNA 3′-UTR shortening is a molecular signature of mTORC1 activation

Jae Woong Chang, Wei Zhang, Hsin Sung Yeh, Ebbing P. De Jong, Semo Jun, Kwan Hyun Kim, Sun S. Bae, Kenneth Beckman, Tae Hyun Hwang, Kye Seong Kim, Do Hyung Kim, Timothy J. Griffin, Rui Kuang, Jeongsik Yong

Research output: Contribution to journalArticle

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Abstract

Mammalian target of rapamycin (mTOR) enhances translation from a subset of messenger RNAs containing distinct 5′-untranslated region (UTR) sequence features. Here we identify 3′-UTR shortening of mRNAs as an additional molecular signature of mTOR activation and show that 3′-UTR shortening enhances the translation of specific mRNAs. Using genetic or chemical modulations of mTOR activity in cells or mouse tissues, we show that cellular mTOR activity is crucial for 3′-UTR shortening. Although long 3′-UTR-containing transcripts minimally contribute to translation, 3-′UTR-shortened transcripts efficiently form polysomes in the mTOR-activated cells, leading to increased protein production. Strikingly, selected E2 and E3 components of ubiquitin ligase complexes are enriched by this mechanism, resulting in elevated levels of protein ubiquitination on mTOR activation. Together, these findings identify a previously uncharacterized role for mTOR in the selective regulation of protein synthesis by modulating 3′-UTR length of mRNAs.

Original languageEnglish (US)
Article number7218
JournalNature Communications
Volume6
DOIs
StatePublished - Jun 15 2015

Fingerprint

3' Untranslated Regions
Sirolimus
Chemical activation
signatures
activation
Messenger RNA
ribonucleic acids
protein synthesis
proteins
Proteins
Ubiquitin-Protein Ligases
Polyribosomes
5' Untranslated Regions
Ubiquitination
Protein Biosynthesis
Ligases
Ubiquitin
mechanistic target of rapamycin complex 1
cells
set theory

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Chang, J. W., Zhang, W., Yeh, H. S., De Jong, E. P., Jun, S., Kim, K. H., ... Yong, J. (2015). MRNA 3′-UTR shortening is a molecular signature of mTORC1 activation. Nature Communications, 6, [7218]. https://doi.org/10.1038/ncomms8218

MRNA 3′-UTR shortening is a molecular signature of mTORC1 activation. / Chang, Jae Woong; Zhang, Wei; Yeh, Hsin Sung; De Jong, Ebbing P.; Jun, Semo; Kim, Kwan Hyun; Bae, Sun S.; Beckman, Kenneth; Hwang, Tae Hyun; Kim, Kye Seong; Kim, Do Hyung; Griffin, Timothy J.; Kuang, Rui; Yong, Jeongsik.

In: Nature Communications, Vol. 6, 7218, 15.06.2015.

Research output: Contribution to journalArticle

Chang, JW, Zhang, W, Yeh, HS, De Jong, EP, Jun, S, Kim, KH, Bae, SS, Beckman, K, Hwang, TH, Kim, KS, Kim, DH, Griffin, TJ, Kuang, R & Yong, J 2015, 'MRNA 3′-UTR shortening is a molecular signature of mTORC1 activation', Nature Communications, vol. 6, 7218. https://doi.org/10.1038/ncomms8218
Chang JW, Zhang W, Yeh HS, De Jong EP, Jun S, Kim KH et al. MRNA 3′-UTR shortening is a molecular signature of mTORC1 activation. Nature Communications. 2015 Jun 15;6. 7218. https://doi.org/10.1038/ncomms8218
Chang, Jae Woong ; Zhang, Wei ; Yeh, Hsin Sung ; De Jong, Ebbing P. ; Jun, Semo ; Kim, Kwan Hyun ; Bae, Sun S. ; Beckman, Kenneth ; Hwang, Tae Hyun ; Kim, Kye Seong ; Kim, Do Hyung ; Griffin, Timothy J. ; Kuang, Rui ; Yong, Jeongsik. / MRNA 3′-UTR shortening is a molecular signature of mTORC1 activation. In: Nature Communications. 2015 ; Vol. 6.
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