title: mRNA 3'-UTR shortening is a molecular signature of mTORC1 activation.
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.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA.
authors.forename: Jae-Woong
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA.
authors.forename: Hsin-Sung
authors.initials: HS
authors.lastname: Yeh
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA.
authors.forename: Ebbing P
authors.initials: EP
authors.lastname: de Jong
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA.
authors.forename: Semo
authors.initials: S
authors.lastname: Jun
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA.
authors.forename: Kwan-Hyun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Sun S
authors.initials: SS
authors.lastname: Bae
authors.affiliation: Biomedical Genomics Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Kenneth
authors.identifier: 0000000188760706
authors.initials: K
authors.lastname: Beckman
authors.affiliation: Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Hwang
authors.affiliation: Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Kye-Seong
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA.
authors.forename: Do-Hyung
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Griffin
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Kuang
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, 321 Church Street, SE 6-155 Jackson Hall, Minneapolis, Minnesota 55455, USA.
authors.forename: Jeongsik
authors.initials: J
authors.lastname: Yong
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D015153:Blotting, Western; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D013058:Mass Spectrometry; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D011132:Polyribosomes / Q000378:metabolism*; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
chemical_list: D020413:3' Untranslated Regions; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; C546843:mTOR protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases