PMID- 26074333 OWN - NLM STAT- MEDLINE DCOM- 20160408 LR - 20211203 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 6 DP - 2015 Jun 15 TI - mRNA 3'-UTR shortening is a molecular signature of mTORC1 activation. PG - 7218 LID - 10.1038/ncomms8218 [doi] AB - 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. FAU - Chang, Jae-Woong AU - Chang JW AD - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA. FAU - Zhang, Wei AU - Zhang W AD - Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA. FAU - Yeh, Hsin-Sung AU - Yeh HS AD - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA. FAU - de Jong, Ebbing P AU - de Jong EP AD - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA. FAU - Jun, Semo AU - Jun S AD - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA. FAU - Kim, Kwan-Hyun AU - Kim KH AD - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA. FAU - Bae, Sun S AU - Bae SS AD - Department of Pharmacology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea. FAU - Beckman, Kenneth AU - Beckman K AUID- ORCID: 0000000188760706 AD - Biomedical Genomics Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. FAU - Hwang, Tae Hyun AU - Hwang TH AD - Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. FAU - Kim, Kye-Seong AU - Kim KS AD - Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 133-791, Republic of Korea. FAU - Kim, Do-Hyung AU - Kim DH AD - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA. FAU - Griffin, Timothy J AU - Griffin TJ AD - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA. FAU - Kuang, Rui AU - Kuang R AD - Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA. FAU - Yong, Jeongsik AU - Yong J AD - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA. LA - eng GR - AG039758/AG/NIA NIH HHS/United States GR - GM097057/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20150615 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (3' Untranslated Regions) RN - 0 (Multiprotein Complexes) RN - 0 (RNA, Messenger) RN - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - *3' Untranslated Regions MH - Animals MH - Blotting, Western MH - Fibroblasts/*metabolism MH - Gene Expression Regulation MH - Mass Spectrometry MH - Mechanistic Target of Rapamycin Complex 1 MH - Mice MH - Multiprotein Complexes/*metabolism MH - Polyribosomes/*metabolism MH - Protein Biosynthesis MH - *RNA Processing, Post-Transcriptional MH - RNA, Messenger/*metabolism MH - TOR Serine-Threonine Kinases/*metabolism MH - Ubiquitin-Conjugating Enzymes MH - Ubiquitin-Protein Ligases MH - Ubiquitination EDAT- 2015/06/16 06:00 MHDA- 2016/04/09 06:00 CRDT- 2015/06/16 06:00 PHST- 2014/09/22 00:00 [received] PHST- 2015/04/18 00:00 [accepted] PHST- 2015/06/16 06:00 [entrez] PHST- 2015/06/16 06:00 [pubmed] PHST- 2016/04/09 06:00 [medline] AID - ncomms8218 [pii] AID - 10.1038/ncomms8218 [doi] PST - epublish SO - Nat Commun. 2015 Jun 15;6:7218. doi: 10.1038/ncomms8218.